PSYC 304 TERM 2

recap of the glutamate synapse and LTP

glutamate synapse can show LTP. When cell is at rest, (hyperpolarized) cat turn on NMDA b/c Magnesium blocks channel from opening but AMPA always working. Then cell fires continuously and NA gets through AMPA and cell depolarizes and excitation kicks off MG from NMDA and Ca influx into the cell through NMDA triggers long term changes -- LTP (synapse is stronger)

what is the limbic system named for?

its location in the brain "edge"

Human Development of Emotion 3 months

joy (will smile, show excitement) • sadness following withdrawal of positive events • disgust

What is a synonym for ovulation?

"In heat," causes changes in behaviour

Actions of Cocaine and Amphetamines

**Normal DA transmission: DA is released by presynaptic terminal, but is quickly taken back by the DA transporter. **Cocaine: blocks the DA transporter, so DA that has been released stays out a lot longer **Amphetamines: Reverses the DA transporter, so more DA is released and stays out a lot longer -Both work on multiple monoamine systems (NE, 5-HT), but reinforcing effects mediated via by actions on DA

ALL DRUGS OF ABUSE THAT HAVE ADDICTIVE POTENTIAL CAN:(2)

- 1) ACTIVATE THE MESOLIMBIC DA SYSTEM - 2) PRODUCE SENSITIZATION

Alcoholics and metablozation of alcohol and genetic polymorphisms

- Alcoholics tend to have higher tolerance, metabolize EtOH quicker: related to levels of the enzyme that metabolizes EtOH - Other genetic polymorphisms associated with alcoholism include: GABA-A receptor, 5-HT transporter, opioid receptors

Three ways we can classify drugs as having a high addictive potential are:

- Common sense (do these drugs appear to be habit forming) - Whether animals will self administer the drug - Physical Dependence

Neural Control of Sleep: the four major players and their functions

-Basal Forebrain: group of nuclei (including parts of hypothalamus) which regulate onset of SWS--> slows the brain down, reduces responsivity to environment -many neurons in this region use GABA as neurotransmitter, supresses activity (inhibitory transmitter) -Pons: group of nuclei which regulate different aspects of REM -Brain activity patterns, shut down of muscles (atonia) -Raphe nucleus sends serotonin inputs that inhibit reticular formation neurons -Reticular formation: group of nuclei which regulate waking and arousal--> works in opposition to basal forebrain, keeps you awake *These brain regions interact to control different stages of sleep

Neural Control of Sleep: Lesioning and stimulating sleep centers

-Lesion reticular formation = persistent sleep -Stimulate reticular formation= rapid awakening from sleep -Projects to basal forebrain (inhibits neural activity there) -Lesion basal forebrain= abolish SWS -Stimulate basal forebrain=induce SWS -Lesion region of pons = Abolish REM sleep, stimulate region of pons= activate REM sleep -Some neurons in this region are active ONLY during REM -Lesion the subcoeruler nucleus (a subregion of the pons) = Loss of uncoupling of motor systems during sleep--> this nucleus is responsible for shutting down motor activity of body, when lesioned animals and people act out their dreams -- not random behaviours acting out things from real life like stalking prey and smoking cig

VMH lesions-- true cause is with axons projecting from paraventricular nuclei

-Neurons in VMH may not be what causes effects. These lesions also destroy axons projecting from the paraventricular nuclei of the hypothalamus. Lesions of these fibers alone also produce hyperphagia and obesity. Electrolytic lesion of VMH destroys neurons in this nucleus AND axons running through--> PVN axons pass through VMH -•Destroy PVN or axons = same obesity and hyperphagia as VMH lesions •VMH not the only satiety center

Animal Models of Depression tests: what are they used for?

-These tests are routinely used to screen for novel antidepressant treatments • However, they do not totally translate to deficits observed in human depressed patients • E.g: depressed patients still "like" sweet foods, if it is presented in front of them- but are less likely to work to obtain them

regulation by insulin

-beta cells of islets of Langerhans release insulin, liver stores blood glucose as glycogen, other cells increase consumption of glucose, leads to decreased blood sugar, regulated by negative feedback

CH 13 TEXTBOOK: hypovolemia

-can be caused by serious blood loss (hemorrhage) -does not change the concentration of extracellular fluid because salt and ions are lost along with the water -the VOLUME of the extracellular fluid is affected- this is detected by baroreceptors (pressure receptors) in blood vessels and heart -brain activates thirst and salt hunger

Behavioural Electrophysiology:

-changes in neural activity resembling LTP that occur after learning - Lateral amygdala and fear conditioning: neurons fire more in response to CS+ after learning (Lecture 17,1, slide 7) - in vitro: train one group rats on fear conditioning task, other groups no treatment (naïve), or the tone is not predictive of shock (unpaired) • remove brains 24 hrs later: only rats that were trained on task show inc in synaptic strength selectively amygdala pathways • Rats that received tones and shocks but were unpaired did not show potentiation - In hippocampus, these kind of results are much harder to obtain because we don't yet understand the patterns of firing that mediate spatial learning

A Triple Dissociation of Memory Systems: Three radial arm maze tasks: conditioned place preference

-learning phase: put them in arm with fruit loops, next day, put them in arm with no food test day? - Go back to arm where you got food before (Pavlovian Learning) - Hippocampal lesion = no impairment - Amygdala lesion = Impairment, no preference for arm that had food before or arm that had no food before - Dorsal Striatum lesion =no impairment

Female study with partners t shirt (Other, more subtle changes in behaviour also occur during ovulation....)

-partners told to wear t-shirt for 2 days to get their scent on it -gave women the tshirt of their partner and identical tshirt worn by other male with his scent on it and told to report which smell they prefer -when not ovulating, they preferred scent of partner, when ovulating they preferred scent of stranger--novel smell

regulation by glucagon

-regulation by glucagon:alpha cells of islets of Langerhans release glucagon, liver converts glycogen into glucose and releases it into bloodstream. Leads to increased blood sugar, regulated by regative feedback.

by roughly what age is sexual orientation fixed?

1 year old. largely due to biological factors

Integrative Hypotheses for Schizophrenia

1) Decreased PFC dopamine/ glutamate reduces activity, (negative symptoms) 2) "Noisy" PFC may contribute to hyperactive dopamine system and also cognitive dysfunction 3) Increased dopamine transmission in accumbens contributes to positive symptoms) • Schizophrenia is not just a simple increase or decrease in brain dopamine, glutamate or GABA levels • Subtle changes in the PFC and other regions (occurring over development) can in turn alter subcortical dopamine transmission • Changes in separate brain regions underlies different symptoms of the disorder

when is the rats critical period for sexual brain development?

1st week after birth

sexual orientation and brain differences study with gay vs hetero males

3rd interstitial nucleus of the anterior hypothalamus is larger in heterosexual males. - problems with samples (many were from AIDS victims--> leads to degeneration of the brain and can cause this area to be smaller). -These findings should be interpreted cautiously.

Twin studies on alcoholism

55% MZ twins, 28% DZ twins are concordant for alcoholism

When is the critical period? for gonadal development

8-15 weeks

which neurotransmitter initiates REM sleep?

ACH

Nicotine and addiction

About 70% of people who experiment with smoking become addicted. - Compare vs alcohol (10%) or heroin (30%). ~ 20% of all attempts to quit are successful for <2 years - Many long term smokers who have limbs amputated due to smoking related diseases usually start smoking days after operation - Tobacco-related carcinogens may inc freeradicals in body, antioxidants like Vitamin C or beta-carotene may help

Marijuana: acute effect

Acute marijuana affects cognitive functions and psychomotor performance. - Impaired performance for a variety of verbal, spatial, time estimation, and reaction-time tasks. - Cannabinoids appear to interfere with all aspects of memory processing. -Basically, if you're stoned, don't expected to do any cognitively-challenging tasks

Alcoholics and being "cured"

Alcoholics never report being cured, they are "recovering alcoholics" ...one drink can send them into relapse

neural sexual development in rats and altering Female sexual behaviour

Altering FEMALE sexual behaviour • Give T to female rat around 1st week after birth = defeminize and masculinize sexual behaviour in adulthood - Females don't show stereotyped behaviours when given estrogens (proceptive behaviours, lordosis) - Administering T to adult females exposed to T neonatally can cause displays of male behaviours (mounting) • Effects in females not observed if T is given after puberty bc there was no T administered in critical period - Neonatal T = organizational effect - Adult T = activational effect • HOWEVER: if you give estrogens to a neonate female, you also see "male" patterns of behaviour in adulthood. HUH?

Anterograde Amnesia

An inability to form new memories after an injury is called Anterograde Amnesia

Human Development of Emotion 4- 8 mo

Anger (frustration) and surprise, fear -can start to anticipate what will happen in their environment-- they have expectations and when they are violated they may show anger, surprise fear etc

The Amygdala and Fear Conditioning: Auditory fear conditioning with rats

Auditory Fear Conditioning: -Freezing natural defensive response for rodents -In the lab, tones easier to deal with than visual cues -so in experiment: they play tone for rat (CS), give the rat an electric shock on its paws following the tone (US), do this several times, then when the tone is played without the shock they freeze (CR) and have increased BP

CHAPTER 16 TEXTBOOK: bovine spongiform encephalopathy

BSE. At some point,feed that contained protein derived from sheep with "scrapie" was fed to some cows in England and cause the cow version of the protein to fold abnormally. -spongiform-- because it leaves the brain spongy -Creutzfeldt- Jakob disease-- brain disorder in humans, leading to demetia and death, that is caused by improperly folded prion proteins; the human equivalent of mad cow disease

Multiple health hazards with chronic use of nicotine (primarily from the smoke):

Cancers of bladder, esophagus larynx, lung, kidneys, mouth, pancreas stomach: Heart Disease; chest pain, labored breathing, wheezing, coughing, more prone to respiratory infections, pneumonia, bronchitis, emphysema.

neural sexual development in rats and altering male sexual behaviour

Castrate males in first week after birth= feminize and demasculinize behaviour in adulthood - Males don't show sexually stereotyped behaviours when presented with receptive female (mounting, intromitting) - Give replacement T, males STILL do not display these behaviours - Administering estrogens/progestins in adult rats castrated neonatally, male rats can display female behaviours • These effects are not observed if rats are castrated after puberty - Early castration = organizational effect - Estrogen/progestin given in adulthood = activational effect

Amnesia

Certain types of brain injury or drugs can lead to impairments in either the encoding, consolidation or retrieval of long-term memories (amnesia) -Amnesia is categorized by what type of information is lost relative to the time of brain injury (2 types)

Human Development of Emotion overview

Children show some emotions at birth, show all of the "basic" emotions by 8 months, and achieve most emotions displayed by adults by age 3.

Animal Models of Depression: chronic mild stress

Chronic mild stress- Subject animals to multiple different types of stressors over 1-3 weeks (so that animals cannot habituate to one form of stress). Can induce a number of "depression" like symptoms

The DA system and conditioned reinforcement

Conditioned Reinforcement: -CS light comes on -reward is presented (e.g.; food) -Levers are inserted to chamber -One lever gives CS light, other gives nothing • Animals will press lever just for the CS, even though lever press never gives reward • Reward-associated cue is now reinforcing, animals will work for it • Give amphetamine: rat responds much more for the conditioned reinforcer • Important point: Rats sensitized to drugs like cocaine respond more for conditioned reinforcement even when tested drug-free weeks after treatment (effects persist) -So, in a hyperdopamine state, the cues exert a much more powerful influence over behaviour

neural firing and alcohol

Depresses neural firing in multiple ways. - Acts as a sort of agonist on GABA receptors - Reduces functioning of NMDA glutamate receptors - Blocks Ca2+ and other ion channels in neurons - Disrupts Second Messenger systems • At low doses, alcohol preferentially suppresses activity of smaller, inhibitory interneurons, has "stimulant"- like (disinhibitory) effects • At higher doses, causes broad-range suppression of larger cortical neurons that mediates alcohol's more disruptive effects -Alcohol also excites DA neurons, but through other mechanisms

What H.M. Cannot Do

Digit Span + 1 Test: present 5 digits, have subject repeat back correctly. Keep adding number of digits to remember until subject makes errors. - Most people can do 15 digits - H.M. can only do up to 8 digits. • Matching to Sample: - Longest delay used is 40 seconds. H.M. had no difficulty if allowed to repeat the letters. Distract him, impairment -this was on the verbal matching to sample test- sample appears (CBT) in center then disappears. There is a delay and then the rest of the pannel lights up and they have to pick the matching tile (CBT) in different location - Impaired on non-verbal version of this test (using shapes). Intervals greater than 5 seconds disrupt his ability to do task b/c he cannot easily use repetition to remember the sample (was repeating CBT to himself, but now it is more difficult to verbally describe a shape)

What device was used to figure out where H.M's epilepsy was occuring?

EEG-- found in medial temporal lobes

Measuring Sleep in the Laboratory: EMG

Electromyogram (EMG): Measures electrical activity of the muscles. - In humans, sleep researchers usually record from under the chin, as muscle tone in this area is a good reflection of tone in the rest of the body.

Gonadal (Sex) Hormones: Estrogens

Estrogens: Estradiol most common

Three phases of energy metabolism: Digestive phase

Food enters gut, gut releases hormones, causes insulin release - Cholecystokinin (CCK) is one gut hormone that stimulates insulin release: secreted in response to high fat/protein content in stomach

Encoding

Getting the info into your brain by translating it into a neural code the brain can understand. - Analogous to typing on your keyboard; keystrokes are converted into electrical signals the computer can understand.

Intracranial Self Stimulation of septum in rats

Given the opportunity, rats will self stimulate using a lever until exhaustion- ignoring food and water until near death • A form of instrumental learning: rat quickly learn that lever provides reinforcement: respond at very high rates (higher rates for self stimulation of striatum than for food) • Multiple brain sites support self stimulation, dozens have been found • Not a ubiquitous phenomenon; some sites do not support self stim, and stimulation of some sites is aversive • All brain regions that support self stimulation are directly/indirectly connected to the mesolimbic dopamine system

set points thought to regulate food intake: glucostatic

Glucostatic Set-Point Theory: Eating is controlled by deviations from a hypothetical blood glucose set-point. Not entirely true

Opiates

High addictive potential; originally used ~ 4000 B.C. - In order of potency; heroin, morphine, methadone, codeine--> typically used as analgesics - Made illegal/controlled in U.S. between 1914-1924

HPG axis

Hypothalamus releases GNRH---> anterior petuitary releases LH and FSH---> Gonads release angrogens and estrogens and progestins---> travels to body tissues and is mediated by neg feedback

Hormones and Human Female Sex Behaviour: androgens

In healthy women, ( T ) levels have been correlated with various measures of sexual motivation. • Following ovariectomy, in women who do have lessen drive for sex, replacement injections of testosterone, but not estradiol, rekindle sexual motivation.

Factors that determine what we eat: learning to eat vitamins/ minerals

Learning to eat vitamins /minerals: animals can learn to choose foods that contain the vitamins/minerals they are lacking. - Give rats fed vitamin B1 deficient diet a choice between "low B1" and "high B1" foods, rat eat more B1 high food - Give rat 10 choices, only one is "high B1", they cannot learn: too many choices makes it difficult to learn - Junk foods: have the flavors, but not the nutrients; it tastes like it could be good for us, but it's not

set points thought to regulate food intake: lipostatic

Lipostatic Theory: Eating is controlled by a hypothetical bodyfat set-point. Not entirely true.

Physiology of Hunger and Satiety: organs involved

Liver can signal brain about what's going on in the bloodstream via vagus nerve- direct neural connection, no hormones involved - Liver receives blood from small intestine and has detectors for glucose and fatty acids

Defining Memory by Type of Info Stored

Long term memory is broken down into declarative (things you know that you can tell others aka explicit) which is comprised of episodce (Remembering your first day of school-- events) and semantic (knowing the capital of France-- factual) The second arm of long term memory is Precedural (things you know that you can show by doing aka implicit) broken down into conditioning (salivating when you see a favorite food) and skill learning (knowing how to ride a bike-- instrumental learning)

Retrograde Amnesia

Loss of memory for events just prior to an injury is called Retrograde Amnesia (information did not get from short-term memory into long-term memory).

Problems with set point theories: testing

Major predictions of set-point theories fail when tested. - Drinking high glucose or caloric drinks before meals doesn't reduce eating significantly. - Reductions in blood glucose levels (insulin injection) or body fat levels (starvation) that increase eating rarely occur normally.

Amygdala and fear conditioning: 4 parts of signalling involved

Medial geniculate thalamus allows the rat to hear the tone and pain fibres recognize bodily pain from the shocks on their paws -the pain regions recieving the shock signal (US) and the medial geniculate thalamus recieving the auditory tone stimulus (CS) send projections to the lateral nuclei of the amygdala. Lateral sends signals to central nuclei of amygdala and central nuclei sends signals to brain stem (freezing behaviour) and hypothalamus (H.R. inc) which initiate autnomic, emotional, and freezing responses

Hippocampus and Spatial Memory in Rats and the Morris Water Maze:

Morris Water Maze: pool filled with opaque water: escape platform hidden under surface - Rat must use spatial cues to navigate to platform - Normal rats learn to find platform quickly - Hippocampal lesioned rats never learn to find hidden platform efficiently (but no impairment if platform is visible) • The hippocampus is critical for learning about relationships between different stimuli

Female (XX) Sexual Development

NO Y chromosome means: NO TESTOSTERONE NO testosterone means: -Wolffian ducts shrink away -Mullerian ducts grow --> Forms fallopian tubes, uterus, part of vagina Starts around week 7 -Forms as phenotypic female

Norepinephrine (NE) Systems and Sleep

Neurons from locus coeruleus also project to peribrachial area; use NE as transmitter •NE inhibits neurons that mediate REM sleep •NE projects widely through brain/cortex; also mediates arousal •REM sleep episodes occur when neurons in the raphe and the locus coeruleus decrease firing, so that peribrachial neurons can increase firing

Sexual orientation

Not the same as identity! -it is whether you are attracted to men or women

Three phases of energy metabolism: Absorptive phase

Nutrients from meal used for immediate energy requirements, excess is stored away - Glucose enters bloodstream, increases insulin release via direct actions on pancreas and via the liver (glucodetectors)

Where do estrogen and androgen come from?

Ovaries: release much more estrogens than androgens Testes: release much more androgens than estrogens • Adrenal Cortex also releases small amounts of these sex hormones as well - Adrenal corticosteroids secretion inhibits release of androgens

Glucose regulation

PANCREAS: regulates blood glucose levels in bloodstream • Two main hormones: glucagon and insulin •Primary action of glucagon is to convert glycogen (stored carbs) into glucose •Pancreas also controlled by vagus nerve: eating causes release of insulin before food hits gut

Neural Circuitry Implicated in Schizophrenia

PFC: Cognitive functions impaired in schizophrenia (decreased glutamate, dopamine, GABA?)-- projects to VTA Nucleus accumbens: Increased dopamine release in schizophrenia; related to psychotic symptoms VTA (dopamine): VTA sends dopamine input to PFC and accumbens -This connectivity suggests that prefrontal cortex can modulate dopamine release in the nucleus accumbens

Summary of Some Anatomically-Dissociable Memory Systems: amygdala

Pavlovian conditioning for appetitive or aversive events (Humans and Rats)

Anorexia Nervosa: psychological theory

Psychological theory: - positive-incentive value for food goes up during starvation - Meals are a disruptive event on the body, intensified during starvation - Meals forced on anorexic patient may lead to conditioned taste aversions; even though they think about the food, competing factors cause them to avoid it

what type of sleep is the most detrimental to lose?

REM

Hippocampus and Spatial Memory in Rats and the radial arm maze

Radial Arm Maze: rat navigates around maze to locate food using spatial cues around room - Rats remember where they've been, do not re-enter arms - Hippocampal lesions impairs performance, rats make more errors by continuing to go back to where they already ate the food

Insight from animal models of schizophrenia: PCP

Rat/primate studies show that repeated PCP: • 1) decreases dopamine release in PFC • 2) causes cognitive deficits on PFC-dependent tasks • These effects persist weeks after drug treatment has stopped • Schizophrenics also show reduced PFC dopamine activity • Different symptoms may be driven by imbalance of DA transmission in PFC (to little) and striatum (too much) -This model can encompasses some of both the positive and negative symptoms of the disorder

Storing

Retaining information over time. - Saving your text on the hard drive.

CHAPTER 16 TEXTBOOK: SAD

SAD: Seasonal Affective Disorder -winter brings a low period with profound depression, may sometimes alternate with summertime mania -in wintertime, these people feel depressed, slow down, sleep alot, overeat -summer: elated, energetic, active, become thinner -predominantly in women, starts early adulthood -phototherapy (light therapy) is fairly effective as treatment -SAD may result from misalignment of melatonin secretion with sleep

Factors that influence satiety: sensory specific satiety

Sensory Specific Satiety: Humans and animals take in more calories if they are given varied (cafeteria, buffet) diet - Satiety can be taste specific: new taste = more consumption - Encourages consumption of varied diets and to take advantage when different foods are abundant - Study: humans asked to rate palatability of 8 foods they try, then given one of foods for meal - When asked again to rate same 8 foods, one they just ate as a meal got lower rating: when given new meal right after, they ate more.

Factors that influence satiety: social influence

Social Influences: Humans and animals will eat more if they are in groups rather than alone - Study: When two individuals eat together, they tend to take "bites" together, eat similar amounts of food

study looking at sensitization in rats

Study: looked at amphetamine effects on locomotion. 2 groups: 1) Gets amphetamine on Day 1 (baseline), 10 days of saline injections, and then same dose of amphetamine again on test day 2) Gets amphetamine on day 1, and then 10 days of amphetamine. Then give same dose of amphetamine again on test day • After repeated exposure, locomotor response is much bigger with the same dose of drug (the response has sensitized). • Locomotor effects of amphetamine due to increase DA release • Opposite of tolerance. Drugs have multiple actions, some can develop tolerance while others sensitize in parallel.

Human Hippocampus and Spatial Memory: London Taxi drivers

Taxi drivers show increased hippocampal activation when recalling taxi routes - Recall of landmarks that drivers did not know rememeber = no hippocampal activation

Prefrontal Cortex and Behavioural Flexibility: Wisconsin Card Sorting Task:

Test behavioural flexibility (ability to change strategies) • Subjects must first sort cards by one stimulus dimension (e.g., number) • Then task switches, patients have to ignore old strategy and switch to new one (eg. shape) - Patients not told what they must do, are only given positive or negative feedback from experimenter (ie: "yes, that is right", "no that is wrong") • Patients with damage to dorsolateral PFC can learn first discrimination • However they cannot switch strategies, keep sorting cards by first stimulus dimension (keep sorting by number) = perseveration. This still happens even they they REALIZE they are wrong and report this

Retrieval

The active processes of locating and using stored information. - Opening up your text from the hard drive.

Cross culturality and facial expressions

There is cross-cultural similarity in emotional expression production, but there are culture-specific differences in display and interpreting emotional faces - Cultural differences may modulate facial expression of emotions (exaggerate, suppress etc)

Neural Basis of Hunger and Satiety: ventromedial hypothalamus

Ventromedial Hypothalamus: Satiety center? - Lesion this nucleus, animals become obese: starts with massive consumption to get to new weight (dynamic phase) then they maintain that weight (static phase) - Problems: give regular or unpalatable chow instead of high fat diet, minimal weight gain; become finicky eaters - Effects are not permanent?? Neural Basis of Hunger and Satiety (I) - Reinterpretation: VMH regulates energy metabolism, not eating. - VMH lesions increase insulin levels (which would increase lipogenesis and decrease breakdown of body fat into usable forms)

Opiates and withdrawl

Withdrawal: 6-12 hrs after last dose, inc restlessness. watery eyes, nose, sweating (flu like symptoms) followed by a fitful sleep for several hours - Opioids depress CNS function; opioid withdrawal is rebound hyperactivity. - The symptoms are typically worst on the 2nd-3rd day and disappear by the 7th day

Male (XY) Sexual Development

Y chromosome means: *SRY GENE = SRY PROTEIN* -Testes form and start to make: 1) testosterone 2) Anti-Mullerian hormone (AMH) -AMH causes Mullerian duct to shrink -T causes Wolffian ducts to grow Occurs around week 7 -dependent on the prescence of T, presence= masculinization! •T masculinizes other structures through development: -prostate gland -scrotum -penis •These effects are aided by dihydrotestosterone (DHT) •Cells in these areas have enzyme 5α-reductase = converts testosterone into DHT •Forms phenotypic male

Sexual Development (in utero)

You learned in high school biology that the two sexes are determined genetically • XX = female -XY = male Not that simple!

circadian rhythms

a pattern of behavioural, biochemical, or physiological fluctuation that has a 24 hour period -generated by endogenous clock -sub region of hypothalamus -- SCN is the biological clock

Theories of Drug Addiction: Positive Reward Model

addicts take drugs for the pleasurable feelings - Problem: addicts can continue to seek/take drugs even if they are no longer giving as good a "rush" they have felt in the past (i.e.: tolerance to the hedonic effects have occurred) - Some drugs (eg; nicotine) do not give as much of a euphoric rush as other drugs (eg: heroin) but are just as addictive

rat breeding

agressive rats are removed from the gene pool and as a result they have become more docile -mice are very aggresive

what was recognized as the first addiction?

alcoholism

what happens to amygdala and hippocampus under stress?

amygdala inc in size, hippocampus dec in size

Instrumental Conditioning

association with a particular action/ motor response and its consequences (i.e.: reinforcement) --> Here the organism can control what happens - Reinforcer: something that increases or decreases likelihood of response occurring again - e.g.; Rat presses lever to obtain food, learning to ride a bike

Sexual Development (Gonadal)

at 6 weeks, the developing fetus is undifferentiated. No SRY=OVARY (cortex produces ovaries and medulla shrinks) Yes SRY=Testes (medulla produces testes and cortex shrinks) -Y chromosome has SRY gene -Encodes for SRY protein -Shows up @ week 7 of development -SRY protein causes TESTES formation -NO SRY = OVARY formation

Human Development of Emotion 2-3 yrs

become able to evaluate behaviour against a standard. Emotions such as pride, shame and guilt emerge. -Development of latter emotions parallels development of frontal lobe functions

primacy effect

beginning of a sequence is remembered better - starts to get into longer term memory

Comparisons of brain are based on ____

behaviour

why do kids lie alot when they are little?

born this way, have to be socialized to tell the truth -social species that rely on eachother

CH 13 TEXTBOOK: how do we lose water normally?

breathing, perspiration, urination- more water is lost than salt -volume of extracellular fluid is decreased but also the concentration of extracellular fluid increases -extracelular saltiness! -injecting hypertonic solution into hypothalamus causes us to drink -there are osmosnesory neurons in several regions of the hypothalamus, incl. preoptic area, anterior hypothalamus, supraoptic nucleus, and organum vasculosum -these neurons are stretchy- they balloon or shrink as the concentration of the extracellular of the extracellular fluid changes- this mechanically opens and closes ion channels to change membrane potential, this info is relayed to other parts of the brain

Animal Models of Depression: Chronic treatment with CORT

can also induce certain "depression-like" symptoms

what are the three things that can happen to STM?

can be displaced, fade away, or be encoded into LTM

Long-Term memory:

can last lifetime of organism, relatively stable - Can be active or passive; Sometimes we study to remember information, other times just witnessing an event will ingrain it in our memory - Potentially unlimited capacity - Information can be forgotten or recalled inaccurately

CH 13 TEXTBOOK: aquaporins

channels spanning the cell membrane that are specialized for conducting water molecules into or out of the cell

what strategy can make STM easier?

chunking. e.g. phone numbers

CH 13 TEXTBOOK: osmolaity

concentration of a solute in a solution

conditioned withdrawal:

conditioned withdrawal: Withdrawal elicited by the drug environment or drug associated cues. Study: looked at morphine withdrawal. 3 groups of rats 1) never received morphine 2) Received repeated injections of morphine in one context, withdrawal test assessed in different context 3) Received repeated morphine in one context, withdrawal test assessed in same context -Withdrawal was maximal when animals were in same context where drug effects were previously experienced • Suggest that exposure to drug -related cues can induce conditioned compensatory responses

Three phases of energy metabolism: Cephalic phase

controlled by the brain: sight, smell, thought of food, or other cues causes conditioned release of insulin because the brain signals the pancreas

CH 13 TEXTBOOK: intracellular compartment

defined area with water contained inside the cells

Human Development of Emotion Birth

distress and contentment

Medial PFC of rats has a function synonymous to the _____ region in primates and human

dorsolateral PFC

Memory

encoding, storing, and retrieving experiences and information.

why do we have emotions?

evoultionary adaption- avoiding predators using negative and avoidant emotions and positive emotions might help us remember things better -they are emergency response mechanisms -shut down other systems in the body like digestion that are not necessary at the moment

Paralinguistic theory:

face is active as communication channel, not just a reflection of internal emotions note: Context plays a large role in determining how a facial expression is interpreted •Show still photos of actors expressing emotions from movies = less agreement on what emotion is being expressed than if shown scene from movie--> deciphering emotion often dependent on context

day to day how stable is blood glucose levels?

fairly stable

chronic stress has detrimental effects examples (bodies not designed to deal with this type of stress):

fatigue, muscle wasting, steriod diabetes, hypertension (high BP), exacerbation of ulcers, psychogenic dwarfism, bone decalcification, supression of ovulation, impotency, loss of libido, impaired disease resistance, apathy, acclerated neural degeneration during aging

CHAPTER 16 TEXTBOOK: benzodiazapines

favored drugs for treating anxiety -diazepam is the most perscribed drug in history -these drugs that combat anxiety are called anxiolytics -they bind to GABA receptors, where they act as non competitive agonists. Causes enhancement of GABA at inhibitory synapses in the brain

Animal Models of Depression: Chronic Social Defeat

have a rat/mouse fight another one- repeated experiences with defeat can induce "depression"

The Hippocampus and Episodic Memory

helps you remember association between place and event, works with the amygdala -patterns of neurons in cortex are firing to encode memory (sensory regions send inputs to hippocampus) Cells firing in hippocmpus and other groups are firing in specific pattern for where you are/ what you see/ where in time. Every individual element and their relations to eachother are important for encoding a whole memory. -Hippocampus keeps record of multiple bits of info about episode and relation to each other: encodes as distinct patterns of activity -Helps consolidate different bits of information linked to a particular memory in the same regions of cortex that originally processed that aspect of the memory -When you remember an episode, same pattern of activation in hippocampus can activate same regions of cortex to trigger recall -Over time, a retrieval cue may be able to activate cortex to retrieve the memory without the hippocampus (Cant do this with new memory) -** easier to remember strange memories or memories out of the norm

what are hypocretin neurons functions?

hold rem sleep at bay, they are not functioning properly in individuals with narcolepsy

2 seperate research groups for orexin and hypocretin

hypocretin- associated with sleeping orexin- feeding behaviour hence it got two names

sexual identity

identifying as a female or male, your concept of self

explanation of early castration in male rats

if castrated before puberty and injected with estrogens and progestins--> lordiosis and female behaviour early castration= organized female brain estrogen/ progestin administation in adulthood= activational effect ** effects are not observed if rat is castrated after puberty, if given T later on they will show normal behaviour because they were organized male (only castrated AFTER puberty) and T will show activation effcts

Short-term memory:

information held for short periods while physiological changes needed for long-term memory are being made - Limited capacity (7 +/- 2 items) - Susceptible to distraction, requires active rehearsal to maintain - The loss of information occur through displacement (something new pushes it out) or through decay. - Info in short-term memory either gets discarded or moves to other stage of memory - Primacy/ recency memory effects support this distinction - Lack of consensus on how long it lasts (seconds to hours)

lesion raphe and what happens?

insomnia. Disrupts your sleep cycle but eventually you will fall back asleep after several days through other mechanisms of the body

CHAPTER 16 TEXTBOOK: phobic disorders

intense, irrational fears that become centered on a specific object/ activity/ situation and the person feels compelled to avoid it

Withdrawal from nictoine

irritability, anxiety, restlessness, constipation, difficulties in sleeping and concentration, increased appetite.

do fear related memories ever get erased?

it appears no. May last the lifetime of the organism

How is our exterior appearance affected?

largely by hormones, not just by genes

liposuction

leptin causes the body fat to be put back on bc you have removed the bodies store of fat and it goes into survival mode

Effects of nicotine in smokers:

less hungry, more alert, more relaxed - Over time, many of the aversive effects of nicotine develop tolerance, whereas some of the "rewarding" effects may sensitize.

Motivational Programs

mainly classified into approach and avoidant -these are actions to achieve your goals -the primary dependent measure is activity in the brain

CHAPTER 16 TEXTBOOK: what is psychosurgery used for?

mainly for depression and anxiety disorders e.g. OCD and cingulotomy

semantic memories

may not remember the source of the information after a period of time has passed

CHAPTER 16 TEXTBOOK: PTSD

memories of unpleasant episode repeatedly plague the victim -genetic component as shown through twin studies with MZ and DZ

Acute stress can be beneficial examples:

mobilization of energy at the cost of energy storage, inc cardiovascualr and cardiopulmonary tone, supress digestion, supress growth, supress reproduction, supress immunity and inflammatory response, analgesia, nueronal responses including altered cognition and snensory thresholds

CH 13 TEXTBOOK: diffusion

moleculs of a substance like salt (solute) dissolved in a quantity of another substance such as a glass of water (solvent) will passively spread through the water because of the random jiggling and movement of the molecules until they are uniformly distributed throughout the glass

Classic PFC task that can be used across species is "delayed response"

monkey example: put food on right/ left and cover it up. Keep changing this and its very fast paced - Animal acquires information, holds it over a delay and then uses it to guide a response • Trials are given in rapid succession with short inter-trial intervals: on each trial, subject needs to distinguish the information to remember on THAT trial vs previous ones - During "response" phase, animal must figure out where food may be based on what it saw • Humans and primates: dorsolateral PFC lesions impairs, even at shortest delay • Rats: medial PFC lesions impairs delayed response

recency effect

most recent thing you heard in a string of items is easier to recall

CH 13 TEXTBOOK: osmosis

movement of water molecules that occurs when a semipermeable membrane separates solutions containing different concentrations of solute and the solute cannot spread itself evenly accross both sides. Physical force that pushes or pulls water across the membrane is osmotic pressure

Gyri of an alcoholic

much thinner, lose neurons during withdrawal

CH 13 TEXTBOOK: why do we drink water?

not just so that the mouth and throat are wet! -this was tested in an animal experiment where the water was diverted away from the esophagus, and they remained thirsty and kept drinking. The body actually monitors how much water we have ingested and stops in anticipation of correcting extracellular volume (we actually stop drinking before water has left gastrointestinal tract and entered extracellular compartment). Experience may teach us this.

Awake period: activity in brain

not much synchrony, parts of brain are doing their own thing, multitasking -why does closing eyes cause higher amplitude? Visual cortex no longer working- neurons are firing more synchronously and less individualized from different regions

social facial expressions

often occur in the context of other people-- e.g. strike at bowling alley, smile when you turn around to see your friends

why do you see masculinizing effects in female rat if there is estrogen supplied to them as a neonate?

once testosterone gets into the brain it is converted into estrodiol by the enzyme aromotaze--- estrodoil exposure masculinizes the brain! This is simply bypassing a step

CH 13 TEXTBOOK: what would happen if there was no salt in the extracellular envionment?

osmotic pressure would drive water into cells, causing them to rupture -amount of water we drink is determined primarily by the number of sodium ions we possess

brain has direct control over glucose levels through the ____

pancreas

CHAPTER 16 TEXTBOOK: abnormal eye movements to screen for Sx?

people who have been diagnosed with Sx have a more difficult time visually tracking moving objects than control subjects. This could potentially be used to identify individuals at risk for developing Sx

smoking and schizophrenia

people with schizophrenia are much heavier smokers than the general population, it enhances their attention through self medication

what type of hormone are glucagon and insulin?

peptide hormones

CHAPTER 16 TEXTBOOK: Bipolar disorder

periods of depression alternating with periods of mania -some patients have rapid cycling (4+ cycles in one year) -men and women equally effected -less severe patients express dysthymia (mild depression) and hypomania, classifieied collectively as cyclothymia -enlarged ventricles -lithium used for treatment, blcocks the manic phases

CH 13 TEXTBOOK: selectively permeable or semipermeable

permeable to some molecules but not to others

Problems with james lange theory

physiological arousal can be similar across different emotions •Emotions can start before arousal does •Predicts that emotions are entirely dependent on feedback from body •Not true: people with spinal cord injuries can still experience emotions

what is one of the hardest foods to break down?

pork!

CH 13 TEXTBOOK: extracellular fluid as a buffer

prevents excessive loss of water of gain of water that could be deadly to the cell --> reservoir of isotonic fluid that provides and accepts water molecules

what is a-fetoprotein?

protein in the blood that acts like a sponge for estrodiol, it can no longer get into the brain once bound by a-fetoprotein

Broadcast DJ and sleep deprivation

purposefully kept himself awake for 4/5 days, experience paranoia and thought people were out to kill him

CHAPTER 16 TEXTBOOK: panic disorder

recurrent transient attacks of fearfulness -temporal lobe abnormalities, temporal lobe volumes seem to be lower but hippocampal volume is normal

CH 13 TEXTBOOK: isotonic

referring to a solution with a concentration of salt that is the same as that found in interstitial fluid and blood plasma (about 0.9% salt)

CHAPTER 16 TEXTBOOK: OCD

repetitive rituals and persistent thoughts that they are powerless to stop -recurrent thoughts or obsessions lead to compulsions to stop the thoughts and feel at ease

sex as reward in female rats "conditioned place aversion"

same experiment with male rat and the two compartments- one that is neutral where nothing happens and one that a male is placed with herself, receptive female -conditioned place aversion! This finding is interpreted as the female finding sex in this fashion aversive -goes to compartment when she didn't have sex

Human Development of Emotion 18-24 mo

self awareness develops; ability to predict emotions of others: embarrassment, empathy, envy

sleep walking happens when?

slow wave sleep

CH 13 TEXTBOOK: hypertonic

solution with a higher concentration of salt than that found in interstitial fluid and blood plasma

CH 13 TEXTBOOK: hypotonic

solution with a lower concentration of salt than that found in interstitial fluid and blood plasma

P300 wave

something suprises you and all your neurons fire together

Gonadal (Sex) Hormones are _____ hormones with _ main classes

steroid, two

CH 13 TEXTBOOK: what does aldosterone do?

stimulates the kidneys to conserve Na+

Theories of Emotions: cannon bard theory

stimulus (bang)--> peception/ interpretation (danger)--> AT THE SAME TIME general autonomic arousal (heart races) and particualr emotion experienced fear) W. Cannon and P. Bard challenged James-Lang •Stimuli in our environment causes simultaneous increase in arousal AND perception of emotional experience •Brain sees stimulus and 1) decides which emotion is appropriate and 2) activates arousal systems of the body •Proposed that both are parallel and independent pathways that do not influence each other •Which one is correct? We had to wait 40 years to find out.

Theories of Emotions: james lange theory

stimulus (bang)--> perception/ interpretation (danger)--> specific pattern of autonomic arousal (heart races, etc.)--> particular emotion experienced (fear) -W. James and then Carl Lange challenged the idea that feelings precede physiological arousal •Stimuli that we perceive in our environment causes the arousal FIRST •The arousal then leads to a perceived emotion; different emotions may be mediated by different patterns of arousal

Prefrontal Cortex and Planning: Dinner Party Problem":

subjects with PFC impairments were given "real-world" planning task •Given 6 errands to run (e.g.: buy loaf of bread, etc) •Also told to get answers to 4 questions (e.g.; price of tomatoes) •Explicitly told not to enter shops unnecessarily finish as quick as possible • PFC damaged patients very inefficient: broke rules (entered unnecessary shops) and failed on many tasks • All patients remembered and understood rules and attempted to comply • NOT a memory deficit, but a deficit in integrating memory to form plan of action

CHAPTER 16 TEXTBOOK: Tourettes

supersensitive to tactile, auditory, and visual stimuli. They twitch, have ticks, sometimes make strange sounds -verbal ticks are actually rare (Swearing) -starts at early age of 6-7, more common in males, often commorbid with OCD and ADHD -partly genetic -thinning of somatosensory and motor cortex -greater density of D2 receptors

where does motivation to do something originate?

the cortex- stratium helps determine the best course of action, which is also influenced by the dopamine system

Sexually Stereotyped Behaviours in rats: females:

the lordosis, darting, hopping, and ear wiggling are stereotyped behaviours specific to normal female rodents in heat

Sexually Stereotyped Behaviours in rats: males

the mounting and intromissions are stereotyped behaviours specific to normal male rodents in response to a receptive female • These behaviours can be used as an index of changes in male and female brain development, and the effect that different hormones can have on behaviour

Consolidation

the process by which information in short term memory is transferred to long-term memory. - believed to involve physical changes in the way neurons are connected to each other in the brain.

Amygdala and Emotion

three main direct connections: Frontal lobes (interprets signals, chooses action), Hypothalamus (initiates autonomic arousal, stress responses),Motor regions (striatum) (initiates actions)

CHAPTER 16 TEXTBOOK: cingulotomy

used to treat OCD by disrupting cingulate cortex connections

mediating strategies

using stratregies to help your memory recall. H.M. kept repeating CBT to himself

who is phinneaus gauge?

worked on the railroad, rod went through his head when trying to put explosive under rock with rod -insulted people due to his brain damage, experienced burst of emotions

Is there overlap in substance addications and behavioral addiction?

yes there is neural overlap in the brain

REM-Sleep Deprivation

• Cognitive effects of sleep deprivation seem due to reduced REM sleep - Effects can be observed by after a few nights of less than normal sleep - Waking subjects up from only REM sleep also has similar consequences - After repeated REM sleep deprivation, subjects have more bouts of REM to recover • Following sleep deprivation, subjects try to make up sleep loss with more REM sleep - After prolonged deprivation, there is increased sleep time for a few days like 14/15 h - More Stage 3/4, at the expense of Stage 2 - More REM events occur over course of sleep recovery - REM episodes also get longer, and/or more intense, individuals become more "efficient" sleepers

Long term sleep reduction study

• Long-term reduction study: subjects reduced sleep time by 30 min every 2-4 weeks until they were at ~4.5 hrs sleep/night • No adverse effects: increased efficiency of sleep (decreased time to fall asleep and awakenings, increased Stage 4 sleep) • 1 year follow-up showed all were sleeping 2-3 hrs less per night

difference between physical and psychological dependence

• Note, the difference between physical and psychological dependence - A drug may not cause physical dependence, but people take it repeatedly to escape from other problems in their lives.

Salience Attribution in Schizophrenia- a PFC GABA connection?

• People with schizophrenia display abnormal fear learning - High comorbidity with anxiety disorders - Inappropriate discriminative fear conditioning: ↓ fear to CS that was paired with shock (CS+) ↑ fear to CS that was presented alone (CS-) - Increased PFC activity when responding to CS- in patients with schizophrenia

Cycle of sleep, stage 1-4 into REM

•These stages cycle 1 to 4, and then back up to stage 2 •Then, brain waves start to resemble Stage 1 or Awake stages (low voltage, mixed frequency); however, burst of rapid eye movements appear: EMG is absent but you see occasional twitch -THIS is REM (or paradoxical) sleep •During REM a number of events occur that are not observed in SWS •Increased and sustained cortical activity •Severely reduced neural responses to sensory stimuli •Vivid Dreams •Complete loss of muscle tone (motor cortex is active, but cannot access musculature)

Menstrual Cycle and human Female Sexual Behaviour

•Women DO SHOW some changes in sexual behavioural patterns during menstrual cycle •Greater probability of having intercourse and achieving orgasm as ovulation approaches •Female orgasm may play a role in assisting fertilization

Summary of Some Anatomically-Dissociable Memory Systems: striatum

(a.k.a. Caudate Nucleus, Basal Ganglia) - Procedural memory/skill/habit learning (Humans); Instrumental conditioning (Rats)

Hallucinogens: Ecstasy/ MDMA

- Amphetamine-type drug, promotes release of 5-HT and other monoamines - Users describe feelings of universal connection, closeness, euphoria, disinhibition, energetic - Most street sources of Ecstasy contain other hallucinogens, such has LSD: distort multiple sensory processes. Most of the rush comes from a combination of different drug actions - Interferes with body temperature regulation: most OD's are due to dehydration - Low addictive potential, but may lead to damage to the 5-HT system

Lower vs higher doses of alcohol

- Biphasic action: lower doses = disinhibition, euphoria, relaxation. - With increasing amounts, slurred speech, disrupted motor coordination, sedation, coma, death

Summary of Some Anatomically-Dissociable Memory Systems: hippocampus

- Declarative Memory (Humans), Spatial/ Relational Memory (Rats)

Androgen Insensitivity Syndrome

- Genetic defect: no functional androgen receptors even though they have XY chromosomes - No effect of T during development: - Testis form (SRY from Y chromosome), but remain internalized - Mullerian duct atrophy (AMH from testes) but Wolffian ducts DO NOT develop (no effect of T) - Female external genitals develop (no effect of T) - During puberty, secondary sex characteristics develop from estrogens released from adrenal glands and testes - Look and behave like XX genetic women on the outside, but no menstruation, no body hair.

Hippocampus and Contextual Memory: contextual fear conditioning in rats

- Give CS tone-shock pairings in one distinct context (context A) • Give CS tone in separate context (B) = - Normal rats show fear freezing - Hipp. lesioned rats show normal fear to tone • Implicit/procedural learning intact • Put rat in shock context (A) with no CS tone = - Normal rats show fear freezing - Hippocampal lesioned rats do not show contextual fear conditioning • Hippocampus involved in remembering relations between contexts and what events that occurred in those contexts - Note: amygdala lesions impair fear learning about both the tone and the context

Basic facial expressions common across many cultures:

- Happiness, surprise, disgust, sadness, fear, contempt, anger, embarrassment - No specific training required to identify them

Human Hippocampus and Spatial Memory: Studies using virtual 3-D environments

- Humans w/ hippocampal damage are impaired when navigating through space and remembering routes - Imaging studies with healthy subjects show increased activity in hippocampus when people learning routes in virtual environment

what can nicotine do that is positive for you?

- Improve attention/cognition in normal subjects, Alzheimer's patients and schizophrenia - Decrease risk of Parkinson's • Drugs are being developed to produce beneficial effects of nicotinic stimulation without addictive properties

Addictive properties of nicotine linked to route of administration

- Inhalation of tobacco smoke caused rapid/pulsatile increase in nicotine in blood/ brain - Nicotine therapies (ie: nicotine patch) causes gradual, sustained increases in blood/brain levels of the drug- not as reinforcing.

Three phases of energy metabolism: in all of these phases...

- Insulin levels are high & glucagon levels are low • These phases promote: - Utilization of blood glucose as energy source - Conversion of excess glucose to glycogen & fat, amino acids to proteins - Storage in liver, muscle, adipose tissue (Fat) • These phases inhibit: - Conversion of glycogen, fat, proteins into usable fuels

Neural Basis of Hunger and Satiety: Lateral Hypothalamus as the hunger center?

- Lesion this nucleus, animals stop eating (aphagia) - Problems: again, effects not permanent: force feed rats for a week, they eventually start eating again - Reinterpretation: LH lesions cause wide range of sensory and motor disturbances, including decreased appetite. Animals have problems with eating, but not lack of hunger.--> it appears to be a problem with the mechanics of eating

Animal Models of Depression tests: Sucrose Preference

- Models "anhedonia". Depression models reduce preference for sucrose solution vs water. - Chronic antidepressants can reverse this effect.

Animal Models of Depression tests: Forced swim (rats/ tail suspension (mice)

- Models "behavioural despair". Immobility thought to reflect passive coping strategy. -Acute antidepressant treatment reduces immobility and increases active coping strategy (swimming, climbing) in normal animals.

A Triple Dissociation of Memory Systems: Three radial arm maze tasks: locally cued-radial arm maze

- NO SPATIAL CUES (curtains around the maze) -4 lights turned on and food is where the lights are turned on. This is stimulus response learning. When rat eats food, light goes off. - Go to arms where a light is on (instrumental learning) • Once rat eats food off a baited arm, light turns off - Hippocampal lesion = no impairment - Amygdala lesion = no impairment - Dorsal Striatum lesion =Impairment, going to spots where the light is turned off and there is no food

Changes in Brain During Sexual Development of rats: Preoptic area (POA) of the Hypothalamus

- Not a nucleus per se, contains a number of subnuclei (a nucleus is a group of similar cells that is differentiated from the surrounding ones) - Lesions of entire area disrupt sexual behaviour, but still have sexual motivation- just mechanisms of copulation are inhibited - Sexually dimorphic nucleus (SDN) of the POA is larger in males than females - T injections in female neonates = bigger nucleus - Castration in male neonates = smaller nucleus - Lesions of this nucleus (ie: the SDNPOA) do not have major impact on sexual behaviour

Klüver-Bucy Syndrome:

- Removal of temporal lobe in monkeys or other animals caused major alterations in behaviour- Lack of fear, strong oral tendencies (put anything in mouth), hypersexuality -monkey actually reaching out to snake rather than avoiding it -in cats they also have no fear and will mount any animal including dogs - Subsequent studies revealed damage to the amygdala is main temporal lobe region involved in these effects - Conclusion: the amygdala is one subcortical region that regulates generation of some emotional responses

Neural Circuits of Emotions: Decorticate/Sham Rage

- Remove cortex, animals can burst into sudden intense rage; undirected - Stimulate subcortical regions can trigger same effect - Conclusion: subcortical structures can regulate some emotions: direction and inhibition of emotions controlled by cortex

How to lose your amygdala:

- Surgical removal to treat epilepsy (this is where the seizures start) - Urback-Wiethe Disease: genetic defect results in selective calcification of amygdala--> neurons in the amygdala die, lumps of calcium replace them

Emotions and Memory Consolidation: Emotional enhancement of memory consolidation mediated by the amygdala

- Train rats on memory task on day 1, test memory on day 2 - Stimulate amygdala with drugs immediately post-training on day 1 = improved memory consolidation tested on day 2 on tasks such as: • Spatial (hippocampal) learning • Instrumental (striatal) learning • Aversive (amygdala) learning • Amygdala can modulate consolidation of memories by other memory systems • Emotional events activate amygdala, which in turn can enhance consolidation of memories (possibly via stress response mechanisms )

Testing the Emotion Theories: Schachter and Singer (1962) tested the theories

- Two groups of subjects; both received epinephrine (increased arousal) - One group told they would feel increased arousal, other group told no effect - Only those not warned of effect reported emotional experience (supports James-Lange, not Cannon-Bard) - However: particular emotion experienced could be altered depending on context • Happy confederate = happy subject • Angry confederate = angry subject - Goes against James-Lange, because arousal was same in both cases • The body can trick the brain into "feeling" emotions

Today's evidence on effect of marijuana

- Typical user is a red-eyed, giggling, somewhat lazy individual who usually ends up seeking food. Preferably something crunchy (hardly an assassin) - No firm evidence that it is a "gateway drug" that leads to harder drug use or that it leads to "amotivational syndrome" - Billions of dollars have been spent to find adverse effects, but they are much less severe than other drugs of abuse (even legal ones)

Reinstatement of Drug Seeking

-A key aspect of drug addiction is the relapse of drug taking after abstinence •Can be triggered by "taste of the drug", cues associated with drug taking or stress •In animals, this aspect of addiction can be modeled with a "reinstatement" paradigm -step 1: train rats to administer drug (cues can be presented with drug infusion) -Step 2: Take rat thru extinction (lever press no longer delivers drug or cues, rats stop responding) Step 3: On test day, NO DRUG IS PROVIDED, but, reinstatement of lever pressing can be induced by... A drug prime (manual injection of the drug)-or- • A stressor (eg; footshock) -or- • Drug-associated cues -cue induced relapse where the rats reinstates its level pressing behavior almost as much as when they were self-administering the drug So, a drug "taste", cues associated with drug, or stress can 1) Increase accumbens DA release and 2) Trigger drug-seeking behaviour

Dopamine and Drugs of Abuse- what it's not

-Acute catecholamine depletion in humans does not affect measures of reported euphoria induced by cocaine -Acute dopamine antagonism does not affect measures of reported euphoria induced by amphetamine -Studies: Depletion of catecholamines or blockade of dopamine receptors in humans does not alter subjective ratings of cocaine/ amphetamine euphoria • It is now relatively well-accepted (by most scientists) that dopamine is not involved in the pleasurable effects of drugs of abuse (or natural rewards)

Steroid hormones REVIEW

-Derived from cholesterol -LIPID SOLUBLE, dissolve in fat -Readily enters cells -Hits receptors both on outside and inside of cells -binds to steroid receptor complex, goes inside nucleus and binds to DNA, leads to Increased gene transcription (protein synthesis) •Steroid hormones work on a much slower time frame (hours to days) because the protein must be assembled and transported to the right place in the body •Their effects are long lasting •Some steroid hormones require a steroid receptor co-factor, which can alter its effect •Some steroid hormones may also work like peptide hormones by acting on membrane bound receptors in brain

Synaptic Plasticity

-The brain is plastic (i.e.: it changes); every time you learn/encode a memory changes occur in neurons in brain - Short term memory can be carried out by cell assemblies, groups of interconnected neurons - Activity driven by an input can start a chain of activation that can continue for some time (reverberatory circuit) that encodes a particular memory--> The same group of neurons can encode different memories, depending on type of input, pattern of activity etc. - If activity in circuit is strong enough/last long enough, long term changes can occur at synapses to make memories more permanent (i.e. same circuit can be activated again at later time) - These are referred to changes in synaptic strength

sexual orientation and early determination studies

-Vast majority of researchers agree that sexual orientation (hetro/homosexuality) is determined early in development, and is due to biological factors • It is near impossible to rule out social factors, but there is no firm evidence to suggest this plays a major role • Prevalence of homosexuality difficult to determine, but in Western countries, typically range between 2-10% • Genetics: Males= 52% of monozygotic, 22% of dizygotic twins both homosexual. • There may be a gene near the end of the X-chromosome (Xq28) that influences male sexual orientation. • Females = 46% monozygotic, 16% dizygotic are homosexual.

Peptide hormones REVIEW

-amino acid chain, protein -Big molecules and/or water soluble; cannot enter cells easily, have an electrical charge -Hits receptors on outside of cell -Not lipid soluble -peptide hormone binds to receptor, causes change of shape of receptor protein (configurational change), second messengers/ enzymes activated (e.g. cAMP), leads to Multiple effects like: Alter protein synthesis, Alter metabolism of cell, Alter neural activity, Ion channels •Actions of peptide / amine hormones on receptors similar to neurotransmitters on metabotropic receptors in the brain •Relative to steroid hormones, these hormones act quickly (second to minute timescale)

CH 13 TEXTBOOK: hormonal responses to hypovolemia

-baroreceptors detect drop in blood pressure, heart decreases secretion of atrial natriuretic peptide (ANP), which normally reduces blood pressure, inhibits drinking, and promtoes excretion of water and salt at the kidneys -brain steps up release of vasopressin from posterior petuitary gland-- induces constriction of blood vessels, also instructs kidneys to reduce flow of water to the bladder -kidneys release renin into circulation triggering hormonal cascade releasing agiotensin ii -- constricts blood vessles, inc blood pressure, triggers release of vassopressin and aldosterone, causes people to drink acts on POA -may also act in circumventricular organs

Dopamine and Animal Models of Drug Reward

-drug infusion pump is used with rats- they self-administer drugs by pressing a lever (tubes are hooked up to their brain) • REDUCING DA TRANSMISSION reduces/abolishes self administration for most drugs (Except for opiates) ‒ Blocking DA receptors also disrupts formation of conditioned place preference for drugs • Responding for drugs of abuse is associated with inc DA release in the accumbens • inc DA release is also associated with natural rewards and their associated cues, and during learning about cues associated with rewards - However, magnitude of DA release by drugs of abuse can be 10x greater than that induced by natural rewards - So, drugs of abuse activate the brain's natural reward learning pathways, but to a much greater (pathological) degree

A Triple Dissociation of Memory Systems: Three radial arm maze tasks: Spatial Radial Maze

-food in all 8 arms - Don't go back to previously entered arm (spatial/relational learning from the spacial cues around the maze) - Hippocampal lesion = Impairment and they go back to the same arms - Amygdala lesion = no impairment - Dorsal Striatum lesion =no impairment

Passive avoidance memory study in rats

-place a rat in a light chamber, dont typically like these because they are nocturnal) and then they move to the dark side several seconds later where they get shocked. -next day: takes a full minute to go to the dark box now because they have learned -BUT if you give them gluttucorticoid agonist they take MUCH longer, about 300 seconds to move to the darker chamber -this is because glutocorticoid helps consolidate their memory

why do we get hungry? Positive-Incentive Theory:

-set point theory has been shown to not be full story- doesnt account for evolution, experimental tests, and other factors of hunger • The anticipated pleasure of eating is the main factor controlling the behavior. • We have evolved to crave food not because we are in a deficit, but b/c we like it (just like sexual behaviour) • Evolutionary pressure has geared mammals to eat as much as they can when food is available • No one factor is singled out as "the" motivation to eat. Some factors include: - Flavor of the food -Variety of foods available - Vitamin/mineral composition of our food -What you learned about food previously - Type and quantity of food in gut -Presence/absence of other people - Blood glucose levels

firing of neurons in rat amygdala in response to tone

-tone does not produce many AP's in amygdala when presented alone. When accompanied by the shock, many action potentials in the amygdala, and now when the tone is played after conditioning without the shock the AP's in amygdala continue firing • Neurons in lateral amygdala show changes in firing to CS tone over the course of learning that parallels emergence of conditioned response - Human Imaging studies = increase activation in amygdala to CS after conditioning

Cognitive Abnormalities in Schizophrenia: brain activation studies with the Wisconsin Card Sorting task

-twins were involved in the study- identical except one had schizophrenia and one did not -put into PET scanner -schizophrenics and discordant identical twin controls performed Wisconsin Card Sort • Schizophrenics showed minimal increase in PFC activity when performing task, unlike controls • Other brain regions were activated similarly in both groups • Schizophrenics show a dramatic disruption in PFC function, but not as much for other cortical regions Schizophrenics also preservate when the new rule is introduced and they show similarities to those with Frontal lobe damage

sex as reward in male rats "conditioned place preference"

-two components of area are distinguishable e.g. their colour, smell are confined to one of the two boxes. There is a neutral compartment where nothing happens. In the other compartment the male is rewarded with a sexually receptive female -- male rat mounts and ejaculates •On test day, rat is allowed to choose between both compartments •Male rats tend to spend much more time in compartment where they had sex. •This is used as an index of reward

Evidence for Aromatization hypothesis:

1) Neonatal injections of estradiol masculinizes behaviour (saturation of all the α-fetoprotein molecules in bloodstream-- much more estradoil is injected than the a-fetorpotein can handle, so it is saturated and then estradoil can enter the brain) 2) Enzyme aromatase is present in neonates 3) Blocking aromatase, or estrogen receptors disrupts masculinizing effects of T 4) Dihydrotestosterone (DHT) cannot be converted to estradiol, has no masculinizing effects 5) Female α-Fetoprotein knockout mice show more male/less female like behavior

Pavlovian (Classical) Conditioning: Five key points

1) The CS must reliably predict the US 2) Delivery of CS and US are uncontrollable to organism 3) The CR is also uncontrollable - Typically an autonomic response (e.g.: heart rate) but can also be motor (Pavlovian approach) 4) In humans, the CR typically occurs in the absence of conscious knowledge. 5) Very long lasting: - Can be extinguished, but reinstated very quickly with another CS-US pairing

Neural Regulation of Male Sex Behaviour: Evidence for Testosterone/Estradiol regulation of male rat sexual behaviour

1) lesions of mPOA or medial amygdala disrupt sexual behaviour 2) stimulation of mPOA initiates sexual behaviour 3) implantation of T into just the mPOA reinstates sexual behaviour in castrated males •Androgens gets these brain regions ready to act in response to sexual stimuli. Do not cause behaviour, but are necessary for it (activational effect).

CH 13 TEXTBOOK: two states that can signal more water is needed

1) low extracellular volume (hypovolemic thirst) due to loss of body fluids e.g. through vomiting or diarhea 2) high extracellular solute concentration (osmotic thirst) e.g. after very salty meal, pulls water out of intracellular compartment

schacter and singer experiment: emotion in response to external stimulus

1) stimulus- inc heart rate, cause person to look to environment for cues - perceptions/ interpretations/ thoughts 2) physiological arousal from epinephrine 3) arousal triggers emotion and affects future interpretation of that stimulus

3 main points to understand about the neural basis of memory:

1) there are multiple forms of memory 2) different types of memory are regulated by distinct brain regions 3) one type of memory is regulated by multiple brain regions interacting

Steps of Digestion (8)

1. Chewing (mastication) 2. Saliva (lubrication) this is where digestion starts! Salivary amylase breaks down starches into simple sugars 3. Swallowing (getting there) 4. Stomach - storage and Breakdown (HCl, Pepsin) alcohol is absorbed here, unlike most other things, food typically stays here for about 4 hours 5. Duodenum - absorption --> may be 6 hours before this point before nutrients actually get into bloodstream 6. Gall Bladder and Pancreas fluids further break down food in duodenum (proteins--> amino acids; starch--> simple sugars). 7. Bile from liver (stored in gall bladder) breaks down fats. 8. Remaining water and electrolytes absorbed by large intestine or ejected via the anus. This whole process takes 18-24 hrs!

study on the sensory stimuli associated with smoking

4 groups: -Sham puffs: unlit cigarette -Nicotine infusions: infusions into blood stream -denic puffs: no nicotine in cigarette -saline infusions -experienced smokers preferred puffing on deniconitized cigarettes over receiving an IV nicotine infusion that mimicked blood nicotine levels produced by cigarette smoke. — Over a lifetime, a smoker will have 100,000s "pairing" with a mouthful of smoke, a burst of nicotine in system (and a burst in DA activity). — These sensory stimuli can become almost as reinforcing as the drug itself.

Theories of Drug Addiction: Physical Dependence Model

Addicts take drugs to get rid of withdrawal symptoms (opposite reaction to drug) - Problems: Addicts often relapse when withdrawal symptoms have passed; some drugs do not have severe withdrawal symptoms (i.e.: cocaine) - Detoxified addicts (drugs eliminated from system) still remain addicted - Treatments used to curb withdrawal (e.g. nicotine patch for smokers) are not 100% effective

Amygdala and Appetitive Conditioning: conditioned reinforcement with rat and light/ female prescence experiment

Conditioned Reinforcement: ("Mana from heaven") -CS light comes on -reward is presented (e.g.; receptive female) -Levers are inserted to chamber -One lever gives CS light, other gives nothing (neither are ever associated with reward). • Rats press lever just for the CS, even though lever never gave reward - Light becomes reinforcing, animals will work for it • After lesions to lateral amygdala: rats show no preference for lever that produces the CS (no conditioned reinforcement) - Yet, they consume reward normally, press levers for food normally, • Previously neural environmental cues associated with reward can control our behaviour, even though we may be unaware of their control

Brain Changes With Depression

Functional imaging studies have revealed: • Increased blood flow to amygdala and ventral parts of medial prefrontal cortex • Dorsal medial PFC (anterior cingulate) actually shows decrease activity. • Some aspects of depression may be caused by disrupted regulation of amygdala emotional processing by certain parts of PFC • Alterations in brain activation can be normalized with antidepressant treatment • Dysfunction of prefrontal cortex may one of the underlying mechanisms that leads to aberrant negative appraisals of life events (everything seems a lot worse than it is)

Alcohol and its toxic effects: Health concerns (5)

Health concerns with alcoholism include: -Acute Toxicity (alcohol poisoning): Lethal dose ~0.45 Blood Alcohol Concentration. Most do not reach lethal blood levels (vomiting at 0.15 BAC, unconsciousness at 0.35 BAC).. these things often stop people from getting to lethal blood levels but can happen if you drink ALOT in a short amount of time. -Also, alcohol dehydrogenase (enzyme for breaking down alcohol) is different in women, they have a different version of the enzyme that is less effective and will increase their drunkness in comparisson to a man of the same size. -Brain Damage (Korsakoff's' Syndrome): Severe anterograde amnesia linked to degeneration of medial thalamus (caused in part by vitamin B1 deficiency). They know they have a problem and will make up stories for why they cannot remember things. - Other brain areas show cell loss that seems to be related to glutamate excitotoxicity that occurs during withdrawal - Liver Cirrhosis: Scarring of the liver - most common cause of death in alcoholics. - Many different types of cancer -Fetal Alcohol Syndrome: Mental retardation, poor coordination, poor muscle tone, low birth weight, deformities.

Neural Abnormalities in Schizophrenia: hippocampus

Hippocampus: Some schizophrenics have enlarged lateral ventricles, due to smaller hippocampus and other temporal lobe regions • Closer inspection reveals organization of hippocampal neurons is altered in the schizophrenic brain (neural organization occurs during development) • Not brain damage per se: changes in the neural organization can disrupt the way brain regions process information -pyramidal neurons are organized in normal fashion, cell bodies point in same direction for controls -pyramidal neurons have haphazard arrangement in schizophrenic patients, their connectivity is latered in the hippocampus

Amygdala and Appetitive Conditioning: human study with memory test and M&M's

Human conditioned preference: subject conducted a "memory task" (find the red or black ball) -Correct response = pleasant tone, with distinct background and a food reward -Error = no tone, no reward, other background -Subjects then shown different patterns, including ones linked to "correct" responses: asked to choose which pattern they prefer -Results: normal humans preferred pattern associated with reward -Right or left amygdala lesions: NO PREFERENCE -When controls asked "why do you prefer this one?"= displayed no conscious association with pattern and reward e.g.: "looks like the sun", "reminds me of pizza", " is a little more complicated", "is symmetrical", "I liked the lines and curves", "was an interesting sort of pattern, caught my eye."

genetic studies on father with children and alcoholism

If father is alcoholic: 25% of sons, 5-10% of daughters likely to become alcoholics

Neural Basis of Hunger and Satiety: Arcuate Nucleus of Hypothalamus

This is the First-pass appetite control center - Satiety and hunger signals from body interact with this nucleus to regulate feeding behaviour - 4 main ones (all peptide hormones): - Pancreas: Insulin ( decreases feeding) -Intestines: PYY3-36 (decrease feeding)--> released from intestines while digesting - Fat Cells: Leptin (decrease feeding) -Stomach: Ghrelin (increase feeding)--> when stomach is empty - Each of these activate different types of neurons in arcurate nucleus • Neuropeptide Y (NPY) & agouti-related peptide (AgRP) -set of neurons that increase appetite - Activation of these cells increase appetite • Pro-opiomelanocortin (POMC) & Cocaine/amphetamine regulated transcript (CART)- neurons that decrease appetite - Activation of these cells decrease appetite

The Stress Response: sympathetic nervous system and HPA

Two main pathways out of brain trigger bodily responses to stress 1) Sympathetic Nervous System: Direct projections from spinal cord stimulate adrenal medulla, causes (nor)adrenaline release Stressor--> brain--> spinal chord--? sympathetic nervous system--> adrenal medulla--> noradrenaline This is a direct neural connection, happens very quickly 2) Hypothalamic-pituitary axis (HPA): Limbic regions (amygdala, hippocampus, frontal lobes) sends signals to hypothalamus that can trigger stress response -Stressor--> Hypothalamus releases CRH into anterior pituitary, which releases ACTH in blood, hits adrenal cortex --> glucocorticoid release (CORT)- in humans this is cortisol that: 1) increase glucose metabolism so sugar can be used better and it gets into cells quicker and decreases inflammation (get body ready for action and/or damage)- dont have time to deal with pain and swelling at the moment, offsets these debilitating effects 2) Reorganizes energy usage

Neural Sexual Development: rats and the brain

Unlike humans (& other animals), rat nervous system develops for a number of days after birth • This includes development of brain regions responsible for male or female sexual behaviour • Like the development of the body, sexual development of brain is governed by the presence or absence of androgens (testosterone, T) • No androgens during critical period= female neural development by default

How are gonadal hormones regulated?

by positive and negative feedback

PFC neural activity and delayed response: occulomotor task

flash box on different parts of a screen and the monkey must keep its eyes focused on the middle of the screen, looking straight during the flash. Then there is a delay period then the box flashes again and monkey must look at the same quadrant where box flashed in order to get food. •Record from PFC neurons: different neurons fire at different parts of task •This activity is resistant to distracters (unlike similar activity in other brain regions) • Delayed period activity predicts accuracy of response (lots of AP's during delay= predict the monkey will do well on this trial.) Lots of activity= better response -Reduced delay activity = animal makes an error

CH 13 TEXTBOOK: extracellular compartment

fluid outside of our cells- divided by interstitial fluid (fluid between cells) and blood plasma (the protein-rich fluid that carries red and white blood cells) -water moves back and forth between this compartment and the intracellular compartment

Principles of Drug Action: Sensitization:

for some effects, repeated exposure increases sensitivity to behavioural effects of drugs

is there one or multiple memory centers in the brain?

multiple

• Effects of nicotine in non-smokers:

nausea, vomiting, coughing, sweating, abdominal cramps, dizziness, flushing, diarrhea.

Basic Nutrients: Vitamins and Minerals

needed to assist in bodily functions - (digestion, cell building, regular homeostasis etc)

Theories of Emotions: Folk psychology

stimulus (bang)--> perception/ interpretation (danger)--> particular emotion experienced (fear)--> specific pattern of autonomic arousal (heart races, etc.) - Old school-common sense view of emotions emphasized that feelings/emotions always precedes the physiological arousal, in a linear sequence

when the adrenal cortex releases high amounts of corticosteroids what happens?

supresses the release of androgens

Gonadal (Sex) Hormones: Androgens

testosterone (T) most common - Dihydrotestosterone: another androgen, much more potent form of T

Testing the Emotion Theories: Capilano Suspension Bridge Experiment:

you can trick body without drugs too - Male subjects meet a female confederate on suspension bridge (high arousal) or on stone bridge or office (low arousal) - Afterwards asked to rate their level of attraction to confederate - Those on suspension bridge rated confederate as much more attractive; more likely to ask her out

Basic Nutrients: Carbohydrates

~4 kcal per gram, glucose is primary fuel of the body, all other carbs get converted to glucose -glucose absorbed by small intestine into bloodstream - Storable form of carbohydrate is called glycogen (glucose molecules strung together) : stored in liver and muscles

Basic Nutrients: Amino Acids

~4 kcal per gram. Comes from proteins, basic building blocks for all cells - 20 amino acids, 9 cannot be produced by body = essential amino acids (come from animal proteins like milk and meat- they are complete proteins) - Amino acids can be converted to glucose

Basic Nutrients: lipids (fats)

~9 kcal per gram. Long term energy source. - Fats can be converted to free fatty acids as alternate energy source for most cells of the body -some evidence that some fats may be equally as efficient as glucose for some activities/ used in conjunction with glucose

Dopamine and Addiction? Putting It All Together

• 1) Addictive drugs dramatically increase mesolimbic DA levels - DA does not appear to mediate the hedonic effects of natural or drug rewards (liking), but plays appears to play a major role in associative learning and preparatory/approach behaviours (ie: wanting) • 2) Drug-induced increases in DA release "trick" your brain into thinking something important is going on, so it starts to make associations with environmental cues linked with drug taking • 3) Cues associated with reward (natural or drug) can also increase DA release in regions like the accumbens - These increases in DA release can trigger the same behaviours that got you the rewards in the first place (drug seeking) • 4) prolonged drug use leads a hyperactive (sensitized) DA system - Increased DA transmission can amplify the effects that drug-related cues exert over behaviour

Prefrontal Cortical Function

• "Thinking is done by the cells of the brain behind the forehead...The cells of the rest of the brain may know how to feel and see and hear, and how to make the body move, and may have wonderful things stored in memory, but if the forehead cells do not know how to think, the mind cannot make use of such memories. • We say that such a person is a fool, even though he has great knowledge.

Treatment Issues and Limitations of the Monoamine Hypothesis (4)

• 1) Antidepressants increase monoamine levels quickly, yet there is a lag in the reduction of symptoms (chronic treatment is required) • 2) Not all depressed patients respond to drugs that increase monoamine levels--> There is a large placebo effect - antidepressants tend to improve symptoms vs placebo in the most severely depressed patients & SSRIs are not more effective than classic tricyclics that effect noradrenaline release as well (but have fewer side effects) • 3) SSRIs associated with increased risk of suicide in children and adolescents (but causal relationship unclear). • 4) In animal models, depletion of 5-HT does not cause a depressive-phenotype - Suggest that there is more to the disorder than merely a overall decrease in 5-HT levels in the brain

Two primary actions of INSULIN

• 1) promotes use of glucose as primary energy source for body - Most cells of body cannot use glucose readily, insulin helps glucose get into cells it is a polar molecule - Brain is one exception: it uses glucose without need for insulin. Only energy source that brain can use is glucose. • 2) promotes conversion of bloodborne fuels to storable forms - Glucose to glycogen in muscles and liver - Glucose and fatty acids to adipose tissue (body fat) - amino acids to protein in muscles

Support for the Dopamine Hypothesis

• ALL drugs are effective in treating psychosis block D2 receptors to some degree - How are D2 receptors being overstimulated? • More D2 receptors? - Unlikely: Some post mortem studies report inc D2 receptors in schizophrenic brains, others failed to find this effect -unmedicated shizophrenic patients have no inc in D2 recptors compared to controls - Changes may be due to chronic antipsychotic medication upregulating dopamine receptors • More dopamine being produced? - Probably not: Schizophrenics do not show differences in dopamine metabolites in CSF • More dopamine being released? - Study: imaging allows for non-invasive measure of dopamine release in human brain - Give amphetamine to schizophrenics or controls - Greater dopamine release in accumbens of schizophrenics - More dopamine release = more positive symptoms •Dopamine release may be hypersensitive in schizophrenia

The Glutamate Hypothesis of Schizophrenia

• Abuse of phencyclidine (PCP, angeldust) or ketamine (Special K) can cause psychotic symptoms and cognitive deficits resembling schizophrenia • These drugs block NMDA glutamate receptors - Block the ion channel: glutamate cannot activate receptor -when given ketamine, inc in positive symptoms, negative symptoms and made more errors like preservation on wisconsin card sorting task -symptoms could persist for a little while after taking the drug -• Glutamate hypothesis: Schizophrenia is caused by decreased glutamate transmission - PFC/hippocampal neurons use glutamate as transmitter - Degeneration of these neurons in schizophrenia disrupts their function, less glutamate released in these areas

How Opiates work in the brainq

• Act as agonists for "endogenous opioid" receptors, peptide transmitters - Enkephalin, endorphin and dynorphin are 3 most common endogenous opioid peptides- generally inhibit neural activity - Endogenous opioids mediate numerous functions (analgesia, emotional regulation, sensory/motor integration) - Receptors in the accumbens mediate pleasurable aspects of natural rewards (sweet/fatty tastes etc) - Opioid receptors are on GABA neurons in the VTA, stimulation of these receptors inhibit GABA neurons, disinhibit dopamine neurons

Stress and Cognition

• Acute stress (or just CORT) can enhance function of memory centers like the hippocampus - Lots of CORT receptors on hippocampal neurons - CORT can increase excitability of these neurons; lead to better memory encoding - Acute stressors can enhance many types of cognitive function (memory encoding and retrieval, attention, short term memory etc). - Part of the cognitive-enhancing effects of acute stress are due to increased release of monoamines in brain (dopamine, noradrenaline).

opiates and "the rush"

• Addictive potential much lower when used for chronic pain (not intravenous) - The rush: when taken I.V., initial wave of intense abdominal orgasmic pleasure that evolves to serene drowsy euphoria - First rush entices the user to do more, tolerance builds up, higher doses needed to get similar effect; never as good as 1st rush - Tolerance to euphoric effects builds up faster than for respiratory suppression = overdose - The pleasurable effects of opioid drugs are driven primarily by stimulation of opioid receptors (DA plays a lesser role vs other drugs)

Types of Aggression

• Aggression defined empirically: behaviours whose primary function is to inflict harm - Predatory: may be viewed as feeding behaviour - Defensive: aggression in response to attack by conspecifics or other species - Social: unprovoked attack at conspecific for establishing/maintaining social hierarchy: in mammals, mostly in males • Most "aggressive" interactions can be viewed as a continuum between aggressive vs defensive behaviours - e.g.: cat's "playing" with mice are actually defensive behaviours; give antianxiety drug, less play time, more efficient killing -more experience with aggressive behaviour toward mouse- less play time

Diabetes Mellitus

• Aka: type 1 (juvenile-onset) diabetes • Pancreas stops producing insulin, excess glucose in blood stream • Brain can use it, but not all, and cells of the body CANNOT use glucose (need insulin to get glucose into them), start using fatty acids instead • Fatty acids not the best energy source for cells, and cells cannot make use of glucose • Thus, diabetics typically eat a lot because cells of body are starving and yet lose weight because they have low insulin • In contrast, obese people often have high insulin levels: more food is stored as fat, appetite returns faster.

Neural Developmental and Schizophrenia and in utero influences on schizophrenia outcomes

• Alterations during development are thought to be major contributing factor to the disorder • In utero influences include: - Poor nutrition during pregnancy - Premature birth/low birth weight - Physical/immune stressors during pregnancy (e.g. mothers catching the flu while pregnant have higher incidence of babies with schizophrenia) • Early developmental insults lead to brain abnormalities in adulthood • Stressors later in life (after puberty) can trigger onset • Genetics inc sensitivity to stressors by mother or child, either in utero or later in life -Some people may have a genetic susceptibility to acquiring the disease, but certain types of stressors needed to trigger it

Testosterone and Aggression: Anabolic steroids

• Anecdotal evidence that steroids increase aggression - T has been linked to aggression, maybe expectation? - Many who use steroids (athletes) may have been aggressive before - Indirect consequence of muscularity- im muscular now so i can be more aggressive! - Steroids much more potent than T; individual differences (personality types) may play a role--? taking T for long periods of time can interfere with other brain circuits to drive aggressive behaviours

Testosterone and Aggression

• Animal studies: Castration in males decreases social aggression • Testosterone replacement reinstates aggressive behaviour • Humans: Not nearly as clean cut a story - Correlational studies with T levels and aggression = inconclusive (some show +/ve correlation, some no effect) - Not eliminated by castration - Aggressive behaviours not reliably increased by testosterone injections (although a slight increase feelings of anger/hostility have been reported)

Pharmacology of Sleep: entihypnotics (stimulants)

• Antihypnotics (stimulants) • Promote release of catecholamines (dopamine, NE) • increase Wakefulness, alertness but will almost totally suppress REM sleep, even at doses that do not effect sleep patterns • Highly addictive • Caffeine • acts as an antagonist to adenosine (adenosine is inhibitory - when active it causes inhibition of cortical activity) • Adenosine is inhibitory transmitter distributed throughout brain (cortex, reticular formation) • Adenosine accumulates with activity in the brain, decreases during sleep. • Caffeine (or theophylline from tea) can block adenosine, increase arousal

defining emotion 4 parts

• At least four different aspects to emotions : • 1) Physiological arousal: displays of somatic and autonomic responses, facial expressions - Emotional reactions can help us respond quickly to emergency event • 2) Motivational Programs: coordinated responses designed to solve specific tasks/achieve specific goals - Generated by distinct brain systems • 3) Actions: typically, emotions cause us to do something - Specific behaviours designed to enact motivational programs • 4) Feelings: subjective labels placed on certain emotional states • Humans experiences all 4 aspects; in animals, we can only assess 1-3

Psychostimulants- Therapeutic Effects

• At lower doses (ie: those used for recreational use) psychostimulants like d-amphetamine (Adderall™) or methylphenidate (Ritalin™) have therapeutic benefits • Powerful stimulant: promotes wakefulness - Amphetamine given to WW II military personnel to reduce their need for sleep - Still prescribed in for some type of sleep disorders like narcolepsy - One key side effect = reduces R.E.M. sleep

Testing the Emotion Theories: Beta Blockers

• Beta blockers: drugs that block peripheral effect of epinephrine can reduce acute anxiety (e.g.; stage fright) - These drugs block β-receptors in body (cardiac) but do not readily cross blood brain barrier

Anorexia Nervosa: biological mechanisms

• Biological Mechanisms - New studies indicate that processing of information by certain brain regions may be altered in subjects with anorexia. - Frontal lobe regions most affected - Certain hormone/transmitter levels related to feeding are reduced (AgRP, NPY, leptin), but these may be compensatory changes to the loss of weight - 5-HT abnormalities have also been linked to anorexia (often comorbid with depression)

theories of sleep: body restoration

• Body Restoration: Being awake disrupts homeostasis; sleep can be time for body to repair itself - For: Growth hormones released during sleep- involved in repair of body - Sleep helps recovery from illness - Prolonged lack of sleep can be fatal - Against: Intense metabolic expenditures during day do not reliably increase amount of sleep needed, only decreases time to fall asleep

Satiety/Hunger Signals: Body to Brain

• Body uses multiple hormones to signal brain to start/stop eating • Food in gut, glucose in blood can initiate signals to stop eating before food is fully digested - From Stomach: CCK, bombesin, somatostatin - From Liver: detects changes in blood glucose, direct input to brain via vagus nerve (non-hormonal) - From Pancreas: Insulin - From Intestines: PYY3-36 (sends fullness signal) - From Fat Cells: Leptin, gives continuous feedback on body's energy stores • Other peptides can stimulate feeding - From Stomach: Ghrelin, levels remain high during fasting, drop during meal (short term)- intiate hunger

Conditioned Withdrawal and Tolerance acting together

• Brain gets conditioned to cues associated with drug taking. These cues trigger compensatory changes in body to prepare for more drug taking - Go to drug context and then don't take drugs = conditioned withdrawal, b/c there is no drug to counteract the compensatory changes which are usually opposite to those caused by drug - Take drug in same context = conditioned tolerance b/c body has prepared itself to counteract drug -summary: initial drug taking= intoxification effect, over time must take more to get the same effect because of conditioned compensatory repsonse and if you enter context where drugs were taken before you may experience conditioned withdrawal

Obesity: causes

• Causes: U.S. twin study: environmental and genetic factors equally responsible for obesity. • Obese subjects have larger insulin response to sight, sound and smell of food (cephalic phase).

Stress and Cognition: Chronic stress and death of hippocampal and prefrontal cortical neurons

• Chronic stress (and chronic increases in CORT) can lead to death of hippocampal and prefrontal cortical neurons - Chronic stress can impair memory formation/ prefrontal functioning - Chronic injections of CORT alone (without stressor) can also lead to neuronal atrophy/cell death and memory impairments in animals - Excessive monoamine release in brain can also impair cognitive functioning (too much of a good thing).

Cognitive Abnormalities in Schizophrenia

• Cognitive deficits in schizophrenia are less dramatic than the psychotic symptoms: however, these deficits may be a core component of the disorder (i.e.: dementia praecox) - Cognitive functioning is the #1 predictor of long term outcome (better function = better prognosis) - Severity of psychotic symptoms not related to severity of cognitive deficits • Seven primary domains of cognition that are affected: -Speed of Processing -Attention/Vigilance -Working Memory -Reasoning/Problem Solving -Visual Learning/Memory -Verbal Learning/Memory -Social Cognition • Many functions mediated by PFC (selective attention, working memory, behavioural flexibility, planning) are impaired in schizophrenia - Most of these types of cognition can be assessed with animal mode

Psychostimulants- Therapeutic Effects: cognitive enhancer

• Cognitive enhancer: enhances multiple forms of cognition -Attention, working memory, memory encoding ― Enhances cognitive function in healthy human subjects and in certain psychiatric disorders (ADHD, schizophrenia) ― Many of these effects are though to be mediated by enhancing DA and noradrenaline activity in the prefrontal cortex ― However, enhancement of these functions comes at the sacrifice of other functions (e.g.; creative thought)

PFC GABA, fear discrimination and salience attribution: Animal models

• Conditioning: Pair one CS with shock (CS+), present a different CS with no consequence (CS-) - On fear conditioning day, rats receive PFC GABA- blockade or control • Next day, present CS+ and CS- - Do rats show fear when presented with a fear-related stimulus • Will GABA-blockade produce similar deficit to schizophrenia? • Reducing PFC GABA: - Decreased fear to CS+ Increased fear to CS- • Patients with schizophrenia also show: - Decreased ratings of uneasiness and skin conductance to CS+ (less fear) - Increased ratings of uneasiness and skin conductance to CS- (more fear) • GABA-blockade produces similar deficits to those shown by individuals with schizophrenia - • Dysfunctional PFC GABA may also contribute to positive symptoms

Neural Basis of Hunger and Satiety: what is the true story?

• Control of hunger and satiety is distributed across many brain regions - Other hypothalamic subregions, as well as amygdala, frontal cortex are also involved

Neural Control of Sleep: procedures completeted to figure out the "sleep centres of brain"

• Cut spinal cord (encephale isole), or right behind pons = normal SWS and REM sleep - must be that Sleep is controlled by brain in front of pons -Cut in front of pons (cerveau isole) = - CONSTANT SWS -NO REM sleep, this determines SWS in front of brain -Lesion basal forebrain= abolish SWS -Stimulate basal forebrain=induce SWS -Neurons in the basal forebrain release GABA in the adjacent tuberomamilliary nucleus to promote SWS -SO REM sleep back of brain, SWS front of brain -GABA inhibts tuberomamilarry nucleus --> promotes SWS

The Mesolimbic Dopamine (DA) System

• DA neurons are projection neurons: all cell bodies located in midbrain, send axons to many brain regions. Substantia nigra sends DA axons to striatum, involved in motor functions • Ventral Tegmental Area (VTA) is the heart of the mesolimbic DA system, sends DA axons via medial forebrain bundle to limbic regions such as prefrontal cortex, amygdala and nucleus accumbens (NAc) region of the ventral striatum -Mesolimbic pathway= axons from VTA (not substancia nigra) -DA is not fast acting because it has metatrobic receptors

deficits from destroyed/ removed amydala

• Deficits include: - Blunted affect and emotional responses (especially FEAR)-- not scared of anything! - Inability to distinguish "fear" faces - Disruption in generation of emotional responses to conditioned stimuli, dont have emotion in response to physiological arousal • Core deficit; inability to learn the emotional significance of external events - Amygdala = learns to tells you what's good or bad in environment - Prefrontal cortex = interprets these signals and chooses appropriate course of action/inaction

Schizophrenia: What is it?

• Described originally by Kraeplein as dementia praecox (early dementia-- loss of cogntive function), and later by Bleuler as schizophrenia (split mind- sometimes rational, sometimes delusional) • Best viewed as a family of disorders,characterized by at least a few distinct symptoms • Positive Symptoms: abnormal behaviours that have been gained - Hallucinations (typically auditory), Delusions (paranoia), thought disorder (bizarre ideologies) = PSYCHOSIS • Negative Symptoms: normal functions that have been lost - Blunted emotional responses, poverty of speech, social withdrawal, anhedonia (Dont experience pleasure), Lack of insight, COGNITIVE DEFICITS -negative symptoms are consistent, psychotic symptoms go up and down

Critical points about sex and its hormonal basis

• Development into phenotypic male or female controlled by PRESENCE or ABSENCE of TESTOSTERONE • NOT controlled by estrogens • Genes play a role, but presences/absence of hormones (testosterone) plays an equal or greater role in what you look like when you're born, depending on what's in the blood stream during this Critical Period •Sex chromosome controls sex of the gonad •GONADAL hormones determines sex of rest of the body

Competition Between Memory Systems: emotional versus neutral memory experiment

• Different learning system can bias behaviour in different directions (behavioural competition) - Hippocampus = spatial learning = exploration, approach novel stimuli - Amygdala = appetitive conditioning = go back to where good things happened -researchers looked at time spent in arm paired or unpaired with food -4 training trials: Hipp. lesioned and normal rats show place preference for arm paired with food -3 training trials: Normal show no preference yet (haven't learned), Hipp. Lesioned show preference for paired arm with food • Sometimes, damage to one learning system can improve learning mediated by another system - Behaviour mediated by hippocampus interferes with behaviour mediated by amygdala: remove hippocampus, amygdala learns quicker

Treatment Issues with Schizophrenia

• Dopamine is heavily involved in motor functions. - Long term treatment with antipsychotics (dopamine blockers) can cause movement (a.k.a extrapyramidal) side effects - Tardive dyskinesia occurs in about one third of patients treated with classical antipsychotics -people dont like to feel these side effects and sometimes stop taking their medication but the side effects may still persist after going off of their meds • grimacing, tongue protrusion, lip smacking, rapid limb/trunk movements; symptoms sometimes continue after discontinuing medication. - Drugs that are more selective for dopamine vs other receptors usually cause the worst side effects • Antipsychotic drugs treat psychosis (delusions, hallucinations); Other negative symptoms rarely improve with typical antipsychotics

What is Dopamine Doing in Schizophrenia?

• Dopamine neurons show increased activity to highly salient/novel stimuli • This increased activity and release may serve as a signal the brain uses to determine what's important or relevant • A hyperactive dopamine system may "tag" normally irrelevant stimuli as important, and impair filtering out of irrelevant stimuli • This leads to "aberrant salience attribution" that may contribute to delusions • Eg: instead of ignoring the angry d-bag whom you don't know, you start thinking they're angry at YOU and are out to get you and working for the CIA, who are controlled by aliens etc... • By reducing dopamine activity, antipsychotic medications are thought to reduce this aberrant salience • Note: often, schizophrenics still report hearing the "voices" when they're on medication, but they no longer bother them

Neural correlates of male orgasm: Dutch study with PET

• Dutch study • Used PET to detect changes in cerebral blood flow during ejaculation. -to minimize motor activity during scan, sexual stim provided by partner through penile stimulation, continued throughout ejaculation. Volunteers head maintained in position with head restrained and had eyes closed • No change: mPOA • Minimal changes: cortex, particularly frontal regions (reasoning) • Decrease bloodflow: amygdala, entorhinal cortex (memory storage) • Increased bloodflow: ventral tegmental area- houses alot of DA neurons, nucleus accumbens- downstream of VTA (dopamine, reward)

Addiction: A Disease ?!

• Earlier views saw excessive drug use/addiction as signs of personal and moral weakness. • The disease model arose from work on alcoholism- dysregulation of brain function caused by repeated drug exposure. - The disease model reduces the sense of guilt in recovering addicts. • Some criticize disease model b/c there are no laboratory tests that can identify the cause/disease, only behavioral observations - All psychiatric disorders are diagnosed by patient's mental and behavioral symptoms!! • Others view addiction not as a disease but as a behavior pattern that results from interactions among many factors. - Emphasizes the role of learning and other cognitive processes in both the development and the treatment of addiction. • Individuals who become addicted may have pre-existing genetic/neural alterations in learning/ cognitive systems, making them more susceptible to being altered by repeated drug exposure and facilitating transition to addiction

Animal Models of Depression: Rewards and lever pressing

• Effort-related decision making: newer "translational" assay: subject must choose between smaller, "low cost" reward and one that requires greater effort to obtain it (eg, more lever presses, more difficult movements) • Rats subjected to acute stress show reduced preference for larger, high cost rewards • Depressed patients show similar profile (when choosing between repeatedly pressing one of two buttons with either their dominant index finger, or little finger on non-dominant hand) • Models the anergia associated with depression • This type of decision making is dependent on dopamine transmission - current research is placing a greater focus on how this monoamine may be related to depression

Other treatments for depression

• Electroconvulsive shock therapy (ECT): one of the original treatments for depression • causes a seizure by passing an electrical current through the brain. • Method of action poorly understood, still used today in extreme cases. • Transcranial magnetic stimulation (TMS) also alters cortical electrical activity-- high intensity magentic pulses, activating certain cortical regions • Deep Brain Stimulation (DBS) - electrode is surgically implanted in brain, very high frequency stimulation given continuously. • Thought to inactivate targeted brain region - DBS in ventromedial PFC or other subcortical areas has been shown to be effective at alleviating depression in treatment resistant patients • No controlled experiments have been done • Ketamine (NMDA antagonist) - can alleviate depressive symptoms after psychotic symptoms subside. Mechanism of action not clear. • Cognitive/Behavioural Therapy - takes a longer time, but just as effective as antidepressant drugs - when used in combination with other treatments, even more effective.

Measuring Sleep in the Laboratory: EEG

• Electroencephalogram (EEG): Measures electrical activity of the brain. -neurons fire action potentials, groups of neurons fire together causing detection of change in electrical potential in a region (measures a bunch of neurons firing at the same time) -amplitude of wave is important- larger group of neurons fire together= bigger wave -frequency of waves: how often we see oscillations, how often action potentials are firing

Measuring Sleep in the Laboratory: EOG

• Electrooculogram (EOG): Measures eye movements. - An electrode placed near the eye will record a change in voltage as the eye moves.

energy conservation theories of sleep

• Energy Conservation: we use slightly less energy when we sleep - Evidence for: smaller animals with higher metabolic rates sleep more - Against: we still can use a fair amount of energy during sleep (e.g: after a meal) so there is not that much savings - Meat eating animals don't show as much of a correlation between mass (metabolic rate) and amount of sleep-- e.g. lions sleep alot because they are meat eating animals, more energy used for breakdown of food

Hormones and Human Female Sex Behaviour: estrogens

• Estrogens: • Human female sexual motivation/behavior may or may not be as tightly linked to estrogens released during menstrual cycle. - HUMAN female are different from most other mammalian species in this respect (animals only show sexually receptive behaviour when in heat, if there is no ovary in animal - no more sexual behaviour) • Ovariectomy does not have reliable effects on either sexual motivation or sexual behavior. - (Only major sexual pitfall may be reduced vaginal lubrication.)

Problems with set point theories: evolution

• Evolution argues against it: - Food availability was inconsistent and unpredictable until recently. - Best strategy was to eat large quantities of food when it's available to store calories for periods when food was unavailable. This is a mechanism we have inherited from the past- causes us to eat when not hungry to store fate for scarce times

Testosterone and Aggression: Confounds with human studies

• Experience can alter T levels; winners show inc T, losers show dec T levels (both animals and humans) - Can be occur even if after a loss of the sports team or political candidate you are backing! • T levels may be related to dominance more than aggression • Many aggressive outbursts in humans are overreactions to "threat"; better viewed as defensive aggression - In animals, T levels not correlated with defense

Physiology of Hunger and Satiety: experiment

• Experiment: inject chemicals that "trick" system to act as if glucose/fat levels are low - 2-deoxyglucose (2-DG) = compete with normal glucose for absorption, but doesn't activate glucose detectors (causes receptors to detect less glucose) - Methyl palmoxirate = disrupts metabolism of fatty acids (prevents break down of fatty acids-> think think theres not a lot of fat in the system). • Inject these drugs into vein from small intestine to liver = immediate increase in feeding • Cut vagus nerve = abolish this effect • Note: brain also has receptors for glucose (but not fats) in a number of regions. - Infusing 2-DG in certain brain regions also stimulates feeding

Menstrual Cycle and Female Sexual Behaviour: Austrian Discotheque study

• Experimenters went to an Austrian discotheques, asked women to - 1) give saliva sample to detect what phase of menstrual cycle they were in - 2) allow experimenters to take picture of them in the clothes they were wearing • Afterwards they digitized photos and took measurements of how much skin was exposed by the women (how much/little clothing they were wearing) • Women ovulating at the time were exposing the most amount of skin (most scantily dressed, wore more sheer clothing etc.) • Some of these measures correlated with testosterone levels -women on bc not allowed in study because they have their hormones ingested daily that cause stabalization and trick the body into thinking its pregnant

Cognitive Abnormalities in Schizophrenia: Eye tracking task

• Eye tracking task: subject must follow moving cursor with eyes on the screen of a computer • Normal subjects: smooth eye movement from left to right • Schizophrenics: jerky eye movements • Brain wave patterns also differ between normal and schizophrenic during this task. • Differences in tracking/ brain function may be core component of deficits in attention and speed of processing

The Amygdala and Fear- what happens if it is lesioned in humans and animals?

• Fear is an adaptive trait - Keeps us away from bad things • Some stimuli evoke an innate fear response (no learning required) - Snakes, spiders, big moving objects, novelty • Animals or humans with lesions to the amygdala display "fearless" like behaviours - E.g.; Primates innately scared of snakes, but lesions of the amygdala abolish this fear • With many other harmful things in our environment, we learn to be afraid of them - Amygdala plays an essential role in learning to be afraid of potentially harmful things

Pharmacology of Sleep: anathetics

• General anesthetics, that cause unconsciousness, produce slow waves in EEG that resemble SWS. -no REM when under general anethetics • Almost all general anesthetics are agonists (turn on GABA systems- stimulate GABA receptors) of GABA-A receptors - Supports idea that some brain system uses GABA to promote SWS.

Left Brain/Right Brain and Emotions

• General perception that right hemisphere plays more prominent role in emotions vs left hemisphere • Both hemispheres play different roles - Stroke victims w/ left hemisphere damage show most depressive symptoms; frontal lobes most sensitive - Right hemisphere lesions = unduly cheerful - Similar effects with unilateral brain inactivation - Depressed patients show decreased activation in left frontal areas • Facial expressions of emotions develop sooner and are greatermagnitude on left side of face (controlled by right hemisphere) • Theory: anterior regions of left and right hemispheres play more prominent roles in approach and withdrawal processes, respectively - Left frontal damage = anhedonia, decrease initiating behaviour - Right frontal damage = decrease withdrawal behaviour, decrease negative emotions -right side of brain is a little quicker to respond to emotional states

Genetic Factors and Depression

• Genetic influences: Concordance rate higher in monozygotic (65%) vs dizygotic twins (20%). - Some linkage to 5-HT related genes (5- HT2A receptor subtype, SERT), but findings difficult to replicate - No single dominant gene linked to affective disorders has been identified • Part of the complications with genetic studies may be that there are different forms of depression. - e.g.; people with early-onset depression (<30 years) have a higher probability of having relatives with depression: those with late-onset (+40 yrs) have a high probability with circulatory problems, it is less genetically related • Genetics can make one more vulnerable, but whether a disorder develops also depends on other factors (like stress)...

Arcuate Neural Circuitry and Appetite SHORT TERM APPETITE INCREASE DURING FASTING

• Ghrelin (Excitatory) released by stomach when empty, stimulates AgRP/NPY neurons (which increases appetite by inbhibiting the PVN cells via NPV) -Ghrelin also activated the POMC/CART neurons (which usually decrease appetite but the AgRP neurons block the actions of alpha- MSH- AgRP acting like an antagonist for alpha-MSH, blocks the receptors, which causes increase of appetite by disinhibiting the LH cells, leading to activation) • Removes inhibition of LH cells via alpha-MSH, leads to activation of LH

Prefrontal Cortex and Extinction of fear Learning in rats

• Give tone and shock pairings = rats freeze to tone • KEEP giving tones with no shock = rats eventually stop freezing (extinction) - Extinction is not "forgetting" ; it is a form of new learning (e.g: the tone is not bad anymore) that suppresses the old response - Fear memory doesn't fade away, it is actively suppressed • PFC damage in rats does not disrupt learning of fear conditioning to cues or context • However, rats with PFC damage take much longer to extinguish fear response during extinction • PFC projections can inhibit neural activity in the amygdala

Glutamate Mechanisms of LTP

• Glutamate: the primary fast excitatory transmitter in the brain • Main glutamate receptors are ionotropic (ligand gated): allow sodium ions to pass through them to depolarize neuron: 2 main types: AMPA and NMDA • Both activated by glutamate • Both allow Na+ to pass thru and depolarize neuron -Only NMDA receptor allows Ca2+ to pass through • If cell is hyperpolarized, NMDA receptor blocked by Mg2+ ions, cannot be activated by glutamate • AMPA receptors are not, can be activated • If AMPA receptors depolarize neuron enough, Mg2+ block of NMDA receptor is removed (voltage dependent Mg2+ block) • Glutamate can now activate NMDA receptor, allows Ca2+ to get into cell

Sleep Deprivation and its effects

• Great variability in how much sleep humans need, and effects of sleep deprivation - Some display hallucinations/paranoia - Most show increased irritability, decreased ability to concentrate, no real effect on IQ tests - Brain regions activated in rested subjects doing arithmetic problems are not active in sleep-deprived subjects - More complex cognition mediated by the frontal lobes are most susceptible to sleep deprivation - Innovative thinking, planning, selective attention, cognitive flexibility - Tasks with high motivation/arousal components are not as affected e.g. people who work in police force, fire department - ALL people show more sleepiness

Health Effects with Chronic use of marijuana:

• Health Effects with Chronic use: No reports of overdose. ― Smoking may damage lungs; reduce testosterone levels in men; Animal studies suggest it may impair immune resistance • Imaging studies: chronic use associated with some brain abnormalities • Chronic users showed reduced activation in prefrontal/amygdala regions in response to emotional faces- deficits in appropriately judging emotional and affective cues? • Recent studies suggest a link between marijuana use & schizophrenia • Marijuana may precipitate development of psychosis in young individuals already at risk of developing schizophrenia • THC has a number of medicinal effects (anti-nausea, analgesia, appetite stimulant, potential antidepressant properties) - Drug companies developing compounds that stimulate cannabinoid receptors for treatment of a number of disorders

Patient H.M.

• Henry Molaison (H.M.) had intractable epilepsy, one generalized seizure a week, originating bilaterally in medial temporal lobes • Decision was made to remove both medial temporal lobes. This included most of the hippocampus, amygdala, and adjacent temporal cortex. • Post surgery: seizures were all but eliminated by the surgery. IQ actually increased from 104 to 118 post-surgery • First and last patient to have a bilateral temporal lobectomy because it severe anterograde amnesia. He cannot form new memories. • He also had some retrograde amnesia for ~3 years prior to surgery • H.M. had normal short-term memory, but couldn't transfer information to long-term memory. Everything was forgotten the moment his attention shifted.

Psychostimulants (Cocaine, Amphetamines)- psychological and physiological effects

• High addictive potential - Psychological effects: increased self-confidence, alertness, energy, makes people friendly and talkative - Physiological effects: motor activation (fidgety) , dec. appetite, dec. need for sleep, inc. arousal, inc. cardiovascular tone • Addicts typically abuse in "sprees"; binges where high levels of intake are maintained for 1-3 days - Sprees end when $$$ runs out or toxicity develops

Alcohol: stats

• High addictive potential: Oldest of the recreationally used/ abused drug • 2/3 of population consumes, 10% become addicted

Nicotine

• High addictive potential: from tobacco • Stimulates nicotinic ACh receptors, inc. neural activity - Nicotinic receptors reside on DA neurons, main pathway that underlies the reinforcing /addictive properties of the drug

Hippocampal "Place Cells" and rats

• Hippocampal neurons fire preferentially when animal is in one particular location - Separate groups of cells encode for different locations in environment - Recordings from multiple neurons simultaneously show that hippocampus forms a "map" of the environment - Manipulations that disrupt place cell firing disrupt spatial navigation and spatial memory - Hippocampal neurons encode relations between different stimuli in the environment -place cells encode specific locations where you are depending on cues -Specific neurons fire in certain locations while other neurons are quiet in this location

sexual orientation and role of hormones

• Hormones: Homo- and heterosexuals do not differ in hormone levels. Adult castration reduces sexual behavior, does not redirect it. -early studies tried to link low T to male homosexuality but it was really due to high cortisol levels of these males because they were "in the closet" causing them to be highly stressed in the 50s • In animals, neonatal castration or perinatal T can cause same sex preference in many species -Homosexual tendencies have been observed in many species e.g. lions, bears

Fatal familial insomnia

• Humans with fatal familial insomnia die within 7-24 months of disorder onset (typically in midlife around 40s) • Autopsy shows degeneration (i.e.; holes) in the brain (likely causal to sleep problems)-- could be due to prions that cause holes in the thalamus- cant get into the rythms of sleep • Actual cause of death seems to be due to general disruption of immune function - pathogens that are not normally fatal take their toll on the body

Pharmacology of Sleep Hypnotics (sedatives) and their problems

• Hypnotics (sedatives) • Benzodiazepines (eg: Valium, Ativan, Halcion) act on GABA transmission - Are not direct agonist, but facilitate binding of GABA to receptor (helps receptor work better, open for longer, enhance action of brain on own transmitter) • Causes decrease in cortical activity • Problems: Tolerance and addiction develops » Can lead to insomnia when taken off drugs » Distort normal pattern of sleep » decreased REM and Stage 4 sleep; increased Stage 2 sleep » Hangover effect; REM rebound • Alcohol works on a similar mechanism: also decreases REM sleep - Alcohol and benzodiazepines can work synergistically to cause death! • Serotonergic drugs are not effective in treating insomnia - However, increasing the brains 5-HT (eg: increased trypophan) can aid sleeping--> if you just give 5HT then it will throw brains balance off, but if you inc brains own 5HT by inc. amount of tryptophan e.g. warm milk, turkey, red wine= sleepier

Glucose and Insulin as Satiety Signals?

• If you lower animal's insulin level, it becomes hungry and eats large meal: give moderate level of insulin, eats much less. Satiety signal? • Not exactly: give LARGE amount of insulin, that converts most glucose to fat, less glucose in bloodstream. • Brain detects glucose deficit, initiates hunger: animals will now eat a large meal just the same • Glucose as a satiety signal? • Not exactly: diabetics have huge amounts of glucose in bloodstream, but they are always hungry • Under normal conditions, blood glucose levels can stay relatively stable for hours, even days, but we still get hungry • MULTIPLE SIGNALS in addition to glucose and insulin regulate hunger and satiety.

Stress and Immunity

• Immune response stimulates different cells, releases certain hormones to fight infection • The CNS influences immune responses and vice versa - Hypothalamus monitors levels of immunity proteins in blood-- it makes you feel sleepy when it detects immunity proteins and encourages you to go to bed - Autonomic nervous system provides inputs to immune organs - B lymphocytes (B cells)=produces antibodies that neutralize pathogens- b cells read the proteins on bacteria, makes complimentary protein that will stick to bacteria protein, inactivates it and prevents it from replicating - T lymphocytes (T cells)=act as killer cells, helper t cells recognize the infection and release cytokines • HPA system suppresses the immune response - Chronic stress reduces circulating levels of both B and T cells - Can be observed after stressor that are severe (maternal separation, electric shock etc.) or somewhat mild (exam stress) - Ulcers associated with chronic stress are actually due to a bacteria present in most people (Helicobacter pylori); many people have it, but stress reduces immune response, allows it to cause ulcers

Hormonal Regulation of Male Sex Behaviour: the effects of T in animals and humans

• In animals and humans, removal of T effects (castration, drugs) will eventually reduce sex drive (you need SOME T) These effects are gradual, slow decline in sexual behaviour - Replacement of T will bring sex drive back to normal levels • However, relative sex drive and T levels are uncorrelated in normal males. T injections do not increase sex drives - (males have more than 10 times what they need)

Hormonal Regulation of Female rat Sex Behaviour

• In female rats, estrogen starts to increase about 2 days before ovulation - One effect of estrogens is they cause brain to make progesterone receptors • A bit later, progesterone starts to increase • When both of them hit a peak, ovulation occurs: - at this point, female is ready to be impregnated, and shows sexually stereotyped behaviours • Both estrogens and progesterone increasing in this order is required for these events to occur. -estrogen spike must occur first then progesterone-- with this order

sexual orientation in humans and hormone levels

• In humans, evidence is much weaker • Lesbians tend to show markers indicative of fetal androgen exposure (eg; longer ring fingers) ─ Early exposure to synthetic estrogens may lead to women being more amenable to same-sex encounters • For gay men, fetal androgen exposure (or lack thereof) data inconclusive • Other indicators not necessary correlated with early hormones also linked to homosexuality (birth order-males born 1st least likely to be gay, boys born thereafter have a higher chance, handedness- disproportionate amount of homo people tend to be left handed)

The Aromatization Hypothesis in rats

• In male rat fetuses and neonates, testes release testosterone • T gets into brain, and is converted to estradiol by the enzyme aromatase (converted IN THE BRAIN) • It is this early estradiol exposure (not T) that masculinizes the brain • QUESTION: Why don't mother's estrogens masculinize female fetuses? • α-Fetoprotein is in blood of male and female neonates - Binds to free floating estradiol, prevents its entry into brain - DOES NOT bind to androgens, T is allowed to enter brain and be converted to estradiol

Rat sexual behaviour

• In rats, a sexual encounter starts with female • Females rats have an esterous cycle, ovulate every 4-5 days (unlike humans, 28 days) •Step 1: During this time, female will display proceptive behaviours- Darting, hopping, ear wigging in front of male •Step 2: Male begins to mount receptive female •Step 3: female eventually arches her back, moves tail to one side (lordosis) •Step 4: Male then intromits (inserts penis) and thrusts •Step 5: repeat steps 2-4 until male ejaculates

Neural correlates of female orgasm

• In women, clitoral stimulation and orgasm are associated with increased activity in the hypothalamus, amygdala, cerebellum, brainstem and (unlike men) the frontal lobes. • Notably, in parallel with men, several sites in the basal forebrain are active during female orgasm, including the nucleus accumbens, implicating the brain's reward system as a key in sexual responses. -in both men and women the reward centres turn on

Dopamine and addiction- an aberrant form of learning: THE incentive- sensitization hypothesis

• Incentive-Sensitization Hypothesis: cues associated with drug taking take over behaviour - Initial drug taking driven by pleasurable effects - Over time, tolerance develops to hedonic effects (liking the drug less), however, effects on the dopamine system and the learning about drug-related cues become sensitized - Drug-related cues (internal, external, contextual, temporal, or stress) activate neural networks (including dopamine system) that trigger unconscious conditioned responses that collectively may be viewed as craving • These conditioned responses make you THINK you WANT the drug • Similar to how food-related cues can make you hungry - The associative memories between the effects of the drug and associated cues become amplified by the hyperdopaminergic state. • Essentially the brain is hijacked by the DA system. Drug cues trigger more craving and then more drug taking, even if the effects of the drug are not as pleasurable

How much sleep do we really need?

• Individual differences: varies among people and with age - Leonardo da Vinci (slept for 15 mins every 4 hours and for 1.5 hours a day) - Older people spend less time in Stage 3 • Reducing sleep time in short term can have consequences, but if sleep reduction is done over a prolonged period, fewer problems

Hallucinogens: LSD

• LSD ("acid") works on the 5-HT system, activating 2A receptors more than normal - 5-HT can act as a filter in the visual system, LSD can interfere with that system to produce visual hallucinations

Cellular Mechanisms of LTP part two

• LTP comes in two phases: • 1st phase: inc in receptors/glutamate release occur quickly (<1 hr) - These changes blocked by NMDA antagonists • 2nd phase: CREB activates protein synthesis, that causes longer lasting changes (>3 Hrs) ― Dendrite shape and size, more ion channels, more dendrites, etc ― These changes go on for hours after initial memory was encoded - These later phase also blocked by protein synthesis inhibitors • Both phases blocked by prevention of Ca2+ entry into the cell • Ca2+ entry is localized- usually stays around point of entry, so only certain synapses/ dendrites on a neuron will change synaptic strength

The Amygdala and Fear Conditioning: Auditory fear conditioning with rats with lesioned amygdala. Does it matter when you lesion the amygdala (before/ after conditioning)?

• Lesions of different subnuclei of the amygdala abolish freezing and autonomic response to the tone (CS) • These lesions do not effect response to shock • Lesions made prior to conditioning (acquisition) or after conditioning (expression) both disrupt conditioned response • Similar results in human with Amygdala damage =disrupted fear conditioning (blood pressure, heart rate)

long term health consequences of opiates

• Long-term health consequences: Main risks of the I.V. user is risk of O.D. (either due to using street drugs of unknown potency or conditioned tolerance effects) and use of secondhand needles • Other health consequences of long-term use are relatively minor: constipation, pupil constriction, menstrual irregularity, reduced libido • Recent work suggest that long-term cognitive deficits are associated with chronic heroin abuse

Marijuana and its action on the body's cells

• Low addictive potential: active ingredient is THC: from cannabis - receptors found all over brain (DA system, hippocampus, PFC, amygdala, accumbens.) - Receptors were found first, then neurotransmitter was discovered: Anandamide, acts as a retrograde messenger (transmitter that goes from post-synaptic neuron to pre-synaptic neuron and activates the CB1 receptor, which inhibits transmitter release - Exact mechanisms for intoxicating effects not fully understood

sleep deprivation long term consequences

• Major health consequences with extreme long-term deprivation • Laboratory animals can die after ~19 days of no sleep

Depression: What is it? When does it occur? Costs to society?

• Major unipolar depression is one of the most common mood disorder, characterized by: - Unhappy mood (more an absence of happiness than increased sadness), worthlessness, guilt, desperation - Loss of interest, motivation (anergia), and appetite, blunted ability to experience pleasure (anhedonia) - Difficulty in concentration, restless agitation • An episode of depression may occur with no apparent cause (endogenous) or can be triggered by external events (reactive) − High co-morbidity of depression w/ many other medical conditions (e.g. diabetes, chronic pain, heart problems) − Symptom clusters vary with individuals; there may be depression subtypes associated with distinct causes and pathophysiologies. • Major costs to individual and society - Dramatically increased risk of suicide (7-15% vs ~1% general population) - Impact on relatives/friends of the individual with depression - Lost productivity costs

Alcohol - Hangovers and Withdrawal

• Many effects of classic "hangover" are due to inc levels of acetaldehyde (alcohol metabolite) or other forms of acute toxicity - Headaches, nausea, and abdominal cramps - Acetaldehyde can be excreted through sweat (exercise) • Dehydration and electrolyte /vitamin imbalance (via frequent urination) also contributes to hangover - Sports drinks/vitamins before bed can help offset • Hangover is also associated with reduced opioid activity - Fatty/spicy foods can increase opioid release • Others hangover effects due to direct effects of alcohol or withdrawal - sleepiness (suppression of REM sleep) , inc sensitivity to bright lights/loud noises, anxiety, high blood pressure, rapid heart rate/breathing, sweating, vomiting. - Some of these effects may be offset by taking more alcohol • Alcoholics (i.e.: those that are physically dependent) have much more severe withdrawal (can be lethal) • Delirium tremens (DTs) can last 2-4 days. Can include hallucinations, delusions, confusion, hyperthermia, convulsions/seizures, unstable blood pressure etc. -darker alc= worse hangover

Why do we get hungry? Set Point assumption:

• Many people may still attribute hunger to an energy deficit. A negative feedback system to maintain homeostasis. Low energy = hunger. • Genetics, environment play a role in establishing set point -this is true to a certain degree, everyones set point varies

Addiction, What Is It? Three main factors

• Many people take psychoactive drugs recreationally, but even if drug use is quite frequent, they can control their intake: heavy drug use does not necessarily mean the person is an addict. • Three main factors we consider to qualify an individual as a drug addict: 1) Habitual drug use that persists in spite of the adverse effects it has on health and social life » May be viewed as a "chronically-relapsing disorder" 2) Drug seeking behaviour: a disproportionate amount of time spent thinking about (craving) and acquiring the drug 3) Physical Dependence: do they suffer from withdrawal from the drug - Probably not major factor contributing to long lasting effects of addiction. - Withdrawal last for a few days, but addiction can last a lifetime

theories of sleep: memory consildation

• Memory Consolidation: Sleep helps us remember information learned during waking - Sleep deprivation can disrupt memory retrieval - Humans display better verbal memory retention and motor memories if tested following sleep - Theories: Passive = waking interferes with memory retention, or sleeping slows down memory degradation - Active = Sleep processes are actively involved in storing memories • Support for active role of sleep in memory consolidation: - More REM sleep (dreaming) after new learning - Increased activity in brain regions associated with learning during sleep - Continuing debate on the role of REM sleep and learning (may aid in learning, but may not be necessary for it) -during sleep brain actively rehearses what it did while learning awake- same brain regions firing

withdrawal symptoms and high/low does effects of marijuana

• Minimal withdrawal symptoms • Technically defined as a hallucinogen, effects include: - Lower, social doses: inc sense of well-being, dreamy state, altered sensory perceptions. - Higher doses: Sensory disturbances, emotional intensification, impaired motor, cognitive speech processes - In some instances, higher doses can produce transient psychotic symptoms (depersonalization, agitation, and paranoia)

What H.M. CAN Do

• Mirror Drawing Task: subject must redraw object from reflection in mirror. • Rotary Pursuit Task: subjects have to keep pen on target that's on a rotating disk. Requires some minimal degree of skill. - H.M.'s performance on the task improved over a 7-day period even though he claimed never to have seen the task before each of the 7-days. • H.M can do any type of skill learning, but cannot recall learning it • He CAN form some types of long term memories (procedural memories) - Patients with damage to the striatum show the opposite pattern of deficits, cannot learn new skills, but remember the events • He CAN ALSO gradually learn new facts (semantic memories), but cannot recall learning them

Animal Models of Depression: learned helplessness

• Models: a number of experimental manipulations may cause some sort of "depressed" condition in laboratory animals -Learned helplessness animal is exposed to a repetitive, inescapable stressful stimulus. After repeated exposure, some more sensitive animals will not escape when given opportunity. — Those that do not escape tend to have cellular/ neurochemical alterations in the brain, (eg: decrease in 5-HT function). — Acute antidepressant treatment can reduce behavioral despair

The Dopamine Hypothesis of Schizophrenia: 1950s-60s-70s

• Most of the dopamine in the brain is produced in small nuclei in the midbrain • 1950s: Chlorpromazine found to be antipsychotic; causes Parkinson's symptoms in normals • Brains of Parkinson's patients found to be depleted of dopamine • 1960's: Drugs that increase dopamine release (e.g.; amphetamine) could induce psychotic symptoms • Chlorpromazine and other antipsychotics found to block dopamine receptors • 1970s: Dopamine receptor subtypes discovered; antipsychotic potency of a drug correlated with binding to D2 receptors (not D1) • THUS, The dopamine hypothesis was born: • Schizophrenia is caused by an abnormal increase in dopamine transmission, leading to overstimulation of D2 receptors

Prefrontal Cortex: Comparative Anatomy

• Moving up evolutionary scale, relative % size of PFC increases: largest in humans • Medial and Orbital regions = emotion regulation • Dorsolateral Regions in Primates = working memory, flexibility, planning • PFC functions develop late in humans (~2-3 years) • The medial PFC in the rat is thought to be functionally analogous to the dorsolateral PFC in primates and humans

Summary of Some Anatomically-Dissociable Memory Systems: interactions between the brains memory centers

• Multiple brain regions can interact to regulate a particular type of memory • However, different brain regions can participate in separate forms of learning & memory, independent of each other - Different learning systems can encode different aspects of the environment in parallel, i.e.: each system learning something different • When we observe that 2 or more brain regions are independently involved in separate forms of learning (i.e.: lesions to one area impair on one task but not others) this is called a dissociation of memory systems

Why is it so freakin' hard to lose weight? Evaluation of different food sources

• NOT ALL CARBS (or calories) ARE EQUAL (glycemic index) • Carbs that have lower glycemic (<100 like whole grains) index digest more slowly, cause less of an insulin spike • Fructose (as in high fructose corn syrup) vs glucose - Fructose doesn't stimulate satiety centers, may increase ghrelin levels • Proteins and whole grain carbs- require more energy to digest (less goes into storage) • Some foods (beef, eggs, beans, fruits, whole grain carbs) and more filling than others (dounuts, cake, chips) • Reducing caloric intake (50-75% of ad lib levels) prolongs life in humans and animals • Intermittent fasting is one method that shows promise for losing weight (2-3 days/week, drop calories from 1800-2500 to 500- 700). Keeps your metabolism guessing • Our current environment is "pathological", not our weight problems - Many times, radical lifestyle change is needed to lose weight

Psychostimulant Toxicity

• Numerous adverse consequences with long-term use - Psychosis, seizures, brain damage to monoamine system, strokes, heart attacks • Brain damage may be the result of strokes (vasoconstriction via inc. noradrenaline release) or DA-induced toxicity (too much of a good thing) • Many stimulant abusers display deficits in cognitive functions mediated by the PFC, which can persist for years after drug abstinence.

Genetics of Schizophrenia

• Odds of developing disorder increases if one has a relative diagnosed with schizophrenia • Highest concordance in identical twins, or if both parents schizophrenic (~50%) • Adoption studies also indicate that there is a heritability component. • These findings indicate • 1) there is a strong genetic component to schizophrenia, but • 2) altered genes are NOT the only cause of the disease • Genetic component not linked to just one gene, there may be dozens that are altered.

A History of Reward Circuits in the brain

• Olds and Milner (1954) wanted to look at how stimulation of reticular formation could affect learning • In a test to see if stimulation was aversive, one rat appeared to find it pleasurable -this rat would continue to try to experience the pleasureable feeling • Dozens of other rats did not show this effect • Olds was trained as a social psychologist and was a bad surgeon (they took x ray of rats head): electrode was in the septum (more than half a brain away) • Other rats with septal electrode implants also appeared to find stimulation of that area rewarding

Cellular Mechanisms of LTP

• Once Ca2+ enter the cell, it activates multiple enzyme pathways (kinases =phosphorylate other proteins) • Ca2+ activates CaM which in turn activates other kinases • CaM Kinase hits latent AMPA receptor (floating inside cell) and inserts in membrane = more receptors -CAM activates Protein Kinase C and Tryosine kinase which in turn activates CREB • Protein Kinase C and Tyrosine Kinase can activate CREB = short term and long term effects • CREB can lead to formation of retrograde messenger (molecule that goes from postsynaptic neuron to presynaptic terminal (e.g., Nitric Oxide) • These messengers promote more transmitter release • increase synaptic strength by both pre and postsynaptic mechanisms

Stress and Testosterone: paratrooper study

• One prominent effect of increased CORT release is decrease testosterone levels - decreased testosterone adaptive because it reduces energy usage mediated by testosterone (muscle building, sperm production, libido etc.) - Parachute training experiment - Effect on testosterone disappears over time (predictable stress not as detrimental) -paratroopers in army, parachute out of airplane, looked at hormone levels over training. 1st day: cort levels very high and decrease in testosterone. 2nd day: cort not as high, testosterone didnt drop this is bc you learn to predict things in your environment, not throwing you out of homeostasis after you have learned.

Prefrontal Cortex and Emotion- orbital/ medial prefrontal damage

• Orbital or medial prefrontal cortex damage: - Language, motor skills, IQ, unaffected - Normal emotional responses to intense stimuli (e.g. pain) - Impoverished (but not abolished) affect; patients show burst of emotions - Inappropriate in social situations • Core deficit; impaired emotional regulation insensitive to the emotional consequences of their actions at the time, inability to view situations from someone else's perspective - Primate studies: lesions of same regions cause disruptions in social behaviour: decreased social interaction and dominance, altered social preference, decreased motor, facial, vocal expressions - Psychopaths display reduced activity in these regions of the brain, may explain why they feel no guilt or empathy - More subtle types of deficits as well cant understand sarcasm, humor -show video of their inappropriate social behaviour later and they realize its wrong

Neurochemistry of Hunger and Satiety: three other neurochemicals that regulate feeding

• Orexin: Produced in lateral hypothalamus (peptide transmitter) -higher leptin causes decrease in orexin - Stimulates feeding behavior when injected into certain brain nuclei. Antagonist reduce feeding behavior - Release of orexin may be negatively modulated by leptin • Cholecystokinin (CCK): released by gut after feeding (particularly after high fat/protein meal) - Promotes satiety by 1)stimulating insulin release and 2)activating vagus nerve to send signals to brain about nutrient content in gut • Endocannabinoids: the neurotransmitters anandamide stimulates same brain receptors stimulated by active ingredient in marijuana - Activation of anandamide receptors in PVN stimulate feeding

Why is it so freakin' hard to lose weight?

• Our metabolisms are geared to prepare for times of starvation - Reduce food intake, metabolism slows down • Many diets work, but for most, you put the weight back on after you go off of it • Low fat diets- problem is people eat more carbs instead. • Exercise helps, but you have to do a lot of it to make a dent in the calories in/calories out equation - 1 pound of fat = 4100 calories!! - We tend to eat more when we're more active - So many factors can trigger hunger irrespective of what our biological energy levels may be

Sleep stage cylces over the course of one night

• Over the course of a night's sleep, cycle repeats 4-5 times. - ~50% is Stage 2 sleep, 20% REM sleep - One cycle typically takes 90-110 minutes - Early in sleep period, you see more Stage 3-4 sleep, but as sleep progresses you see less Stage 3-4, and longer REM episodes • Sleep (in particular REM sleep) is NOT a state of neural quiescence!

Prefrontal Cortex and Planning

• PFC keeps track of /helps plan sequences of action (Temporal Organization of Behaviour) - e.g: cooking a meal: you have to remember all the ingredients and actions, and put them together in a set sequence - Patients with PFC damage can remember all the ingredients, but cannot carry out various steps in proper sequence - PFC lesions = patient remembers particular items (long term memory intact) but cannot order them correctly • PFC damage impairs recalling the temporal order of events in memory - Ask patient "Which movie did you see most recently, Pulp Fiction or Anchorman" - They can remember seeing both movies, but cannot remember where in time they saw them

Arcuate Neural Circuitry and Appetite: SHORT TERM APPETITE DECREASE AFTER MEAL

• PYY (from intestines in response to meal), inhibits AgRP/NPY neurons • Inhibition of these neurons • Increases PVN activity-- increasing appetite inhibiting function • Allows alpha-MSH to inhibit LH, decreasing LH appetite stimulating function • Other signals from body, and inputs from other parts of brain can regulated activity of these cells

Factors that influence when we eat: Pavlovian Conditioning:

• Pavlovian Conditioning: Environment cues associated with eating can elicit hunger and feeding - Hunger can be caused by expectation of food, not energy deficit - Study: Give rats 6 meals/day at irregular intervals; with each meal, rat gets a tone. - On test days, food is continuously available and they are full after they have eaten but rats will eat in response to tone, even if they had just eaten recently. -similar study with dogs and bell paired with meat powder, caused salivation

Principles of Drug Action: pavlovian conditioning and conditioned tolerance

• Pavlovian conditioning can heavily influence tolerance/withdrawal - Drug effects can serve as conditioned stimuli. Brain will make associations between the drug effects and the context where they occurred • Conditioned tolerance: Tolerance is maximal when drug is administered in environments similar to those where drug effects were experienced previously. • Study: Alcohol causes hypothermia. Give rats 20 shots of alcohol in one environment (over 20 days). On test day, one group gets alcohol in same context (Context A), other group gets it in different context never associated with drug (B). - Animals who received test day in same context displayed tolerance, those in different context did not

LTP as a mechanism for memory?

• Pharmacological studies: drugs that block LTP formation also disrupt learning - Block NMDA receptors during learning in: - hippocampus = disrupt spatial learning - amygdala = disrupt fear conditioning - striatum = disrupt instrumental learning • Treatments immediately after training do not disrupt memory formation • Blocking protein synthesis also disrupts different forms of learning - Treatments immediately after training DO disrupt memory formation − Longer term changes in neurons occur for some time after initial learning • Gene studies: using knockout mice, deletion of genes that encode for enzymes involved in LTP disrupts multiple forms of learning - CaM and other kinases, CREB; many studies show that if you get rid of protein you can disrupt learning and LTP in same animals

H.M. Summary

• Poor performance on long-term memory but not on short-term memory tasks - supports the two stage model for memory formation. • Main problem is consolidating new memories from short-term to long-term storage. - Suggests that memories are stored elsewhere, but that the hippocampus is important for converting memories to long-term storage • H.M. shows learning on some types of tasks (e.g. skill learning). Thus... - 1) not all types of learning and memory are mediated by the hippocampus - 2) memory systems can be dissociated by the type of information being stored, as well as how long it lasts

predatory avoidance sleep theory

• Predator Avoidance: sleep may have evolved to keep us out of trouble - Against: many alpha predators sleep a lot

Neural Abnormalities in Schizophrenia PFC

• Prefrontal Cortex (PFC) pyramidal neurons of schizophrenics have reduced #of dendrites; reduces processing power of these cells. • Hypofrontality (reduced PFC function) is a characteristic negative symptom of schizophrenia • GABAergic interneurons: serve as a major information filter for PFC (and other regions like hippocampus) • Schizophrenics have reduced GABAergic interneurons in these regions • This may lead to a "noisy" cortex, reducing information filtering and impairing functioning of these regions -there are significantly fewer dendritic spines (Where synatpic contacts are made) in people with schizophrenia

Factors that influence when we eat: Premeal hunger

• Premeal Hunger: Time of day that one usually eats can trigger hunger - Can be viewed as a special type of Pavlovian conditioning - Eating at regular times can condition the body to prepare itself for incoming food (cephalic phase) - "Hunger pangs" are the body getting ready for incoming food, not the body craving food

Factors that influence satiety: previous experience

• Previous experience about the nutritive value of certain foods can influence satiety. -brain keeps record of how calorically dense food is • Sham eating experiment: Food is chewed and swallowed and then passes out of the body. Rats given either normal lab chow (which they are used to) or novel food • With normal lab chow, rats start off eating same amount as before surgery. Novel food, they eat more. -Rat eats same amount even though not going into stomach, new food- rat eats more because brain hasn't figured out how much nutrients are in it

Recreational Drug Use vs Drug Addiction

• Psychoactive drugs have been a part of human culture since antiquity. - Many animal species will ingest psychoactive substances e.g. cats and catnip, bees and certain flowers, chimps can get hooked on cigarettes • Many psychoactive substances (nicotine, caffeine, morphine, cocaine, THC), are made by plants and were available to ancient peoples. - A 2011 US Survey estimated that 8.7% of population were current users of illicit drugs. - Legal drugs such as tobacco and alcohol are consumed even more widely. • YET... occasional recreational use can transition to frequent, habitual use in spite of adverse health /social/familial/occupational consequences • The "paradox" of addiction: How can a person develop and maintain a pattern of behavior that is so obviously destructive to his or her life? - No one has a complete explanation for this paradox, though many theories have been proposed.

Insight from animal models of schizophrenia: NMDA antagonists

• RECENT FINDINGS: Doses of NMDA antagonists that induce psychosis/cognitive deficits preferentially reduce activity of GABAergic interneurons (and produces a "noisy" cortex) • NMDA receptors are also on GABA interneurons- blocking these receptors reduces their activity - Negative/cognitive symptoms = decreased glutamate/dopamine/GABA transmission in PFC - Positive symptoms = increased D2 receptor stimulation in accumbens -NMDA antagonist injection= PFC GABA interneuron firing decreases -and PFC pyramidal neuron firing increases

PFC GABA Regulation of Subcortical Dopamine and Cognition

• Reducing GABA transmission in PFC (with the antagonist bicuculline) increases dopamine neuron activity and release in the striatum/nucleus accumbens • Reducing PFC GABA transmission in animals can also causes cognitive deficits that resemble those observed in schizophrenia (attention, working memory, behavioual flexibility) • Thus, reduced PFC GABA activity in schizophrenia may contribute to both the hyperactive dopamine system and cognitive deficits associated with the disorder.

Instrumental Conditioning and the straitum

• Regions of the striatum (part of a larger subcortical system called the basal ganglia) regulates action selection and instrumental conditioning - Striatum receives inputs from sensory/motor cortex and dopamine system. -Instrumental learning goes through phases - Early in learning = goal-directed, responses are made to obtain a goal - Late in learning = responses become more automatic (habitual) --> mediated by dorsal striatum - The transition from goal-directed to habitual actions is mediated by the dorsal striatum • The amygdala sends input to the striatum and can influence instrumental action

Reinstatement of Drug Seeking and disruption

• Reinstatement of drug seeking induced by these triggers can be disrupted by lesions or blockade of DA receptors in prefrontal cortex the accumbens, or the amygdala • Repeated exposure to drugs alters the functioning of these brain regions, making them more sensitive to these triggers • Showing human addicts cocaine related cues/videos elicits intense cravings • These cravings are associated with activation of the same brain regions involved in reinstatement (prefrontal cortex, amygdala, accumbens, VTA)

Sensitization of the Dopamine System

• Repeated exposure to all drugs with a high addictive potential (like cocaine) can induce sensitization of DA release -After repeated exposure to cocaine, rats show more locomotion to same dose they had in the first trial--> same does causes increase in locomotions "sensitization" - Also repeated exposure enhances DA release to reward-cues--> same amount administered shows inc in DA "Sensitization" • Studies in humans have shown these effects can be long lasting! Humans were given continuous doses of amphetamine over 5 trials. The Dopamine release increased each trial even at the 5th trial when they were tested a year later -So, repeated drug exposure can put you into a hyperdopamine state Can lead to sensitized DA release in response to cues associated with drug

how many people have schizophrenia and when is onset?

• Roughly 1% of all people suffer from schizophrenia at any given time - Onset is typically after puberty (18 yrs). - Typically does not onset after 30 in men, small number of women develop symptoms after menopause (+45 yrs)

Mesolimbic DA and Reward

• Self stimulation increases DA release in the limbic system, particularly the accumbens • DA antagonists or lesions reduce self-stimulation • Administration of DA agonists systemically or into accumbens can establish a condition place preference • Animals will work to have DA agonists infused directly into accumbens • Natural rewards, or conditioned stimuli associated with rewards increased accumbens DA release • ALL DRUGS OF ABUSE with high-addiction potential either directly or indirectly increase DA release

Sensory and temporal stimuli associated with the act of smoking

• Sensory and temporal stimuli associated with the act of smoking become conditioned to the reinforcing effects of nicotine and thus function as conditioned reinforcers. - DA plays a key role in mediating conditioned reinforcement - Tobacco companies would study/manipulate sensory qualities of tobacco smoke to enhance the experience (make it more habit forming) - Time can serve as a cue to trigger cravings desire to smoke ramp up around times when smokers expect to be smoking

Neurochemistry of Hunger and Satiety: Seratonin 5HT

• Serotonin (5-HT): a major brain satiety signal • 5-HT neurons in raphe nucleus project to multiple cortical/subcortical areas • 5-HT agonists or releasers (Prozac) in humans and animals can: decrease feeding, even with cafeteria diets decrease amount of food consumed per meal but not number of meals -Shift food preference away from fatty foods -suggest that 5-HT acts as short term satiety signals associated with meal consumption Brain regions: 5-HT inhibits release of NPY in the PVN of hypothalamus, which then disinhibits PVN neurons to promote satiety *5-HT drugs such as fenfluramine have been used to treat obesity with some success: yet heart disease side effect caused it to be taken off market

Neurochemistry of Aggression: what is really going on??

• Serotonin- a negative correlation between serotonin and aggression exists: -The most aggressive monkeys in a free ranging colony had the lowest levels of serotonin. -Mice lacking certain serotonin receptors are hyper-aggressive. -Other neurochemicals implicated in various forms of aggression: • GABA- Pharmacological enhancement of GABA transmission reduces aggressive behavior in humans playing a computer game against an "opponent" who was taking money from them. -options in the game: boost own points, block the other person from taking your money, take points from other person--GABA induced more defensive and recuperative behaviours • A variety of peptide hormones [oxytocin, vasopressin, endogenous opioids], have been implicated in the control of aggression. -oxytocin is the hugging hormone, more agressive with low oxytocin

Problems with set point theories: factors ignored that stimulate eating

• Set-point theories ignore factors that stimulate eating - Taste of food (eg; dessert) - Social factors (going out with friends even though you're not hungry).

Limitations of the Dopamine Hypothesis (5)

• Several findings challenge the dopamine hypothesis 1) Antipsychotics block dopamine receptors right away, yet drug treatment takes ~2 weeks to reach full effect - If schizophrenia is merely an increase in dopamine, drugs should work right away - **More recent research suggests that the drugs may reduce psychotic symptoms relatively quickly, but it takes time for treatments to reach full effect. (measured by surveys like: are you still experiencing hallucinations? how intense are they? etc) 2) Not all schizophrenic patients respond to drugs that block dopamine receptors - If schizophrenia is merely an increase in dopamine, drugs should work for all patients 3) Dopamine blockers can alleviate psychosis, but do not treat negative symptoms - If cognitive deficits are due to an increase in dopamine, these drugs should alleviate the symptoms 4) Some drugs that reduce symptoms do not block D2 receptors that well • Example: Clozapine (atypical antipsychotic) • Not as effective at blocking D2 receptors as classical antipsychotics - Less likely to produce motor side effects • Has a much higher affinity to other receptors, like serotonin (5 HT) • Can improve negative symptoms (possibly via 5 HT blockade) - If positive and negative symptoms are merely due to overstimulation of D2 receptors, atypical antipsychotics shouldn't work as well • Treatment issue: some patients have an adverse blood reaction to clozapine; not all patients can take it safely -Racloprode= typical antipsychotic, it is very "Sticky" to the D2 receptors -Clozapine= atypical antipsychotic, less "sticky" to D2 receptors, binds more to seratonin receptors. Sometimes have benefits for the negative symtoms and cognitive defecits -atypical psychotics typically make the patient gain a lot of weight and can affect hormone levels in males and make them grow breasts 5) Drugs that increase dopamine release can improve negative symptoms • Study: Schizophrenics and controls tested on a working memory task (dependent on PFC function) • Given either placebo or low dose of amphetamine (a dose that increases dopamine release, but not psychotic symptoms) — Note: higher doses of amphetamine do exacerbate symptoms • Under placebo, schizophrenics performed worse than controls • Amphetamine, improved performance in schizophrenics, up to control levels -If schizophrenia is just an increase in dopamine, then why should a drug that increases dopamine release improve cognitive functions?

Defining Sleep: 4 components

• Sleep can be characterized by 4 phenomenon: • Reduced Movement - walking, talking, and running generally preclude a diagnosis of "Sleep". • Stereotypic Posture - Usually we are laying down or in a reclined position when we sleep. • Reduced Response to Stimulation - we are not aware of low-intensity sounds or touches that we would normally be aware of when awake. • Reversibility - We know we can awake from sleep, distinguishing it from a coma or death.

DA as the pleasure molecule? Not so much!

• So drugs of abuse or "natural rewards" increase DA release, so DA = "reward", right? • "Reward" has 2 components - "Liking" = pleasurable, hedonic effects of the reinforcer - "Wanting" = craving, willingness to work for the reinforcer • Studies investigating role of DA in hedonic effects of natural rewards show that it is not - Lesions of DA system does not reduce reactivity (sensitivity to reward); increasing DA (with amphetamine ) also doesn't affect it • DA system appears more involved in the preparatory/approach behaviours associated with rewards and conditioned stimuli, NOT their pleasurable effects • So, dopamine helps get you to the good things in life (wanting), but doesn't seem to be involved in you liking them ― Endogenous opioids (e.g.: endorphins) seem to play a main role in pleasurable aspects of rewards

Social Stress and Testosterone: primates

• Social stress: chronic stressor common in primates - Subordinate males typically have higher CORT levels, lower testosterone levels, shorter lifespans - Dominant males do not necessarily have higher levels of testosterone, but do show faster recovery of testosterone levels after stressor (vs subordinates) - Repeated social stressors (fights) can lead to long term reductions /increases in testosterone in losers/winners - Even more subtle social stressors (e.g.;giving a talk) induces large CORT release in humans -subordinate males live shorter lives than the alpha

Marijuana: history of use

• Some history: Use dates back 6000 years ago to Far East • One story about Muslim sect headed by Hashishin-i-Sabbah - Story goes Hashishin would send out assassins and reward them with cannabis (but was likely opium) • Hemp plant was big cash crop, used for rope and other products • Psychoactive effect introduced in U.S. in the 1920's • In 1926, report in New Orleans newspaper exposes "menace of marijuana": claims that drug turns normal people into violent drug-crazed criminals who become heroin addicts • U.S. gov't enacts laws, listing marijuana as a narcotic, makes it illegal

Long Term Potentiation

• Step 1: Stimulate presynaptic axons @ low frequency (1/15 sec) to get subthreshold EPSP (no action potentials), establish baseline • Step 2: Stimulate axons at very high frequency (i.e.: tetanus, 100 Hz) and get lots of action potentials in post synaptic neuron • Step 3: axons at low frequency again, same subthreshold current = • MUCH BIGGER EPSP than before • Input has become stronger (potentiated), larger EPSP, more likely to evoke action potential

Emotions and Memory Consolidation

• Strong emotional states can enhance memory consolidation; may be mediated in part by noradrenaline -same sequence of slides in study shown to all participants - Normal subjects show better memory for "emotional" vs neutral stories attributed to the same sequence of pictures - Beta-adrenergic receptor antagonists (beta blockers)= selectively reduces better memory for emotional part of story (not other parts) even though they still report emotional response to story - An exaggerated type of memory modulation like this may underlie Post-Traumatic Stress Disorder

Factors that influence when we eat: study with rats and blood glucose

• Study: rats provided unlimited food and water • Blood glucose levels monitored constantly • Glucose levels remain constant through day • A drop in blood glucose (~10%) occurs only before feeding is initiated by rat • Unlikely that drop in glucose is directly responsible for feeding b/c: • No meal: glucose levels go back to their previous homeostatic levels. • Decline may be related to INTENTION to eat, not the other way around. Change was preceded by increase in blood insulin, so drop may have been actively produced rather than a decline in reserves. • Changes in glucose levels may contribute to feelings of hunger, but does not seem to control eating behavior

Imaging the Emotional Brain

• Study: subjects told to recall intense emotional episodes (anger, happiness, fear etc). - Measured skin conductance/heart rate (physiological arousal)- sweat when experiencing an emotion - Use PET to image brain activation during different emotions - Results: Physiological responses came before reporting an emotional response - Same brain regions can be involved in different emotions - Different patterns of activation/ inactivation in multiple brain regions for different emotions • Different emotional states appear to be mediated by distinct patterns of activity in distributed brain regions these results support the james lang theory

• Is 8 hours/night sleep the "right" amount? Study focusing on sleep and mortality

• Study: track mortality rates of adults (with no other sleep disorders) over 10 years • Organize data by how much sleep individuals normally got per night • Results: Those who slept either less, or more than 7 hours tended to have higher mortality rates (bigger effects with 9+ hrs) • Note: Correlational evidence • There may be numerous other facts as to why those who sleep more than 9+ hours may die sooner than those sleep less • However, this shows that getting less than 8 hours/night does not appear to be the risk of life and health as it is often made out to be

Narcolepsy

• Sudden intense attacks of sleep - Patients go directly from waking state to REM sleep - Attacks come on during periods of intense emotion - Loss of muscle tone (cataplexy) during attack - Regular sleep stages when they choose to go to sleep • Causes: Disruption in neural circuits that mediate REM sleep - Has a genetic component: gene that encodes for peptide neurotransmitter hypocretin (aka: orexin) is involved: humans with narcolepsy lose ~90% of hypocretin neurons - Hypocretin neurons in hypothalamus project to sleep-centers (basal forebrain, reticular formation, locus coeruleus) • Treatments: NE and 5-HT agonists to reduce attacks. Development of orexin-like drugs continues

Ways To Change Synaptic Strength

• Synaptic strength typically measured by changes in post synaptic potential evoked by an input - increase strength = larger EPSPs evoked in postsynaptic neuron • 1) inc transmitter release • 2) inc # of receptors or inc receptor sensitivity • 3) Both 1 and 2 • Other types of physical changes in neurons can also occur (change in shape, # of dendrites etc) that can affect the way the post-synaptic neuron responds to input • Note: the exact opposite changes can occur too, decreasing synaptic strength

Factors that determine what we eat: Taste preferences/ aversions

• Taste preferences/aversions: Some tastes have innate high incentive values (sweet, salty, fatty foods)- babies like sweet tastes and dislike bitter- like people do not originally like the taste of beer (same with spicy food but we grow to like it because the slight pain of eating it releases endorphins= pleasurebale) • Others are learned from experience or social situations - give animal novel food, then give toxin to make it sick, animal learns to avoid food (conditioned taste aversion)- only takes one time!

Addiction- medical definitions from DSM 5

• The American Psychiatric Association stopped using the terms "addiction" and "addict". • The Diagnostic & Statistical Manual of Mental Disorders (DSM) defines substance related disorders as: -The individual has manifested a maladaptive pattern of substance use for at least 12 months that has led to significant impairment or distress, by clinical standards. At least two additional criteria must be met: e.g. neg personal consequences, missing school/work

Amygdala and Appetitive Conditioning: Rewarding stimuli for rats

• The amygdala also regulates Pavlovian conditioning for rewarding stimuli - Conditioned response typically approach behaviour (e.g,; conditioned place preference) - The "place" where reward was received becomes attractive --> elicits approach towards those stimuli (Pavlovian approach) - Lesions of the lateral amygdala disrupts conditioned place preference for all types of primary rewards (food, sex, drugs) • Note: lesions of lateral amygdala do not disrupt consumption of primary reward (food, sex, etc) - Only interferes with how conditioned stimuli linked with primary reward affect behaviour

dexamethasone suppression test

• The dexamethasone suppression test can show excessive CORT release • Dexamethasone, a synthetic glucocorticoid, can suppress CORT release in normal people, but not in depressed patients. • Dexamethasone can "fool" the HPA axis into believing there are higher levels of CORT than normal - through negative feedback, levels drop in normals • In many depressed patients, negative feedback mechanisms are disrupted.

Diversity of Symptoms in Schizophrenia and DSM characteristsics to have diagnosis of schizophrenia

• The presence of at least one of three core symptoms is required for diagnosis (DSM-5) - although symptoms vary greatly -Hallucinations, delusions or disorganized speech • These symptoms also present in other conditions that need to be ruled out before schizophrenia is diagnosed - Lack of insight 97% -Auditory hallucinations (not spheech just sounds) 74% - Delusions of reference (innocuous event interpreted as salient) 70% -Verbal hallucinations 70% - Suspiciousness 65% Flatness of affect 65% - Paranoid state 64%

Why do we have to eat? three reasons

• There are many reasons why we eat, but the most fundamental answer is we eat to maintain energy levels of the body • Body uses energy in 3 primary ways: • 1) Basal metabolism: 55% of energy usage is to maintain body heat and other resting functions like breathing, heart rate and brain function - Can vary as a function of body weight • 2) Active behavioural processes: 12-13% of energy usage is for behaviours other than rest e.g. talking, walking, running - Can vary greatly depending on activity levels (use more here, then less in basal metabolism) • 3) Digestion of food: 33% of energy usage is to processes food, break it down into molecules to be used by body • Any remainder typically gets stored as energy reserves

Bypassing the Hypothalamic Feeding Circuit

• This satiety circuitry can be bypassed by cues associated with feeding • Rats given food + auditory cue that predicts foods delivery • Present cues in sated rats, they eat more (Pavlovian conditioned feeding), but... • Lesions to prefrontal cortex or amygdala, or disconnection of the amygdala-LH pathway abolishes conditioned increases in feeding. • NOTE: NORMAL feeding patterns unaffected, only cue-induced feeding disrupted • Other cortical and subcortical brain regions feed into the LH, can bypass the effect of satiety signals from the body -the prefrontal cortex and amygdala are activated by cues associated with feeding and they both work on the lateral hypothalamus to produce increased appetite/ feeding

The Monoamine Hypothesis of Depression-- evolution of the research

• Three major monoamine neurotransmitters are 5-HT, noradrenaline and dopamine • 1950-60s: Reserpine (drug that reduces monoamine levels) induces depression. This drug was first used to treat high BP (it depletes vessicles so monoamine oxidase eliminates the NT) • First monoamine oxidase inhibitors (which block metabolism of monoamines and increase brain levels) alleviated depression • First tricyclic antidepressant (Imipramine, which blocks monoamine reuptake so they can stay in the synapse for longer) also found effective • 1980s: Fluoxetine (aka-Prozac™) a -selective serotonin reuptake inhibitor (SSRI) found to be effective at treating depression • All of these findings support the monoamine hypothesis: Depression is the result of abnormal reductions in brain monoamine (mostly 5-HT and noradrenaline) levels

Long Term Potentiation: to get it you need...where was it originally observed and where can it be seen now?

• To get LTP, you need • 1) simultaneous activity in pre and postsynaptic neuron - Depolarize postsyn. neuron with no presyn. activity = NO LTP - Activate presyn neuron but block postsyn. firing = NO LTP • 2) Very strong (i.e. high frequency) stimulation - Stimulate neuron to get same # of action potentials but at lower frequency = NO LTP • Effect is long lasting (can last months in some studies) • Originally observed in hippocampus in vivo but has been seen in all brain regions that have glutamate synapses - Cortex, amygdala, thalamus, striatum, cerebellum • LTP has been observed in vivo and in vitro, anesthetized or awake animals

Principles of Drug Action: Tolerance (the two types)

• Tolerance: Decreased sensitivity to effects of drug after repeated use. Two types: - Metabolic (Pharmacokinetic): Body (liver) becomes more efficient at metabolizing drug, less drug gets to sites of action - Functional (Pharmacodynamic): occurs at site in brain/body where drug exerts its effects (eg; receptor # decreases) • Tolerance develops to some effect of drugs, not others, and can develop at different rates for different effects - eg: heroin causes euphoria and can suppress respiration. - Tolerance to pleasurable effects develops faster than to respiratory effects. Addicts increase dose to get bigger high, wind up overdosing.

Parallel and independent processing of different memory systems: cross maze

• Train to always enter one maze arm, always turn lef/ west from southern location - Rats can use either a place / spaical cues (hippocampal) or response "turn left, i did it this way before" (striatal) strategy • On probes, release from new start point in the Northern tip , see where rats go • Early in training: Most control rats use hippocampal strategy (8days of training) - Inactivate hippocampus through local anathetic Lidocaine= many rats shift to using striatal strategy • Late in training (16 days): Most rats use striatal strategy - Inactivate striatum = most rats shift to using hippocampal strategy -note: spacial cues were present on both test and practice days • Thus, • 1) different memory systems can learn independently and in parallel to each other • 2) Suppression of one system allows behaviours driven by another to emerge • 3) Different systems learn at different rates (hippocampal = rapid, striatal = more gradual)

Obesity: treatment

• Treatments: - Exercise and proper diet. - Low calorie diets (often give immediate results, then but then weight comes back on) - Appetite suppressants, surgical procedures (drastic, last resort)

Anorexia Nervosa: treatments

• Treatments: very few effective treatments - Less than 30% show long term recovery - ~ 10% die of starvation or suicide

Stages of Sleep: two main classes

• Two main classes: Slow-wave sleep (SWS) and Rapid Eye Movement (REM) Sleep •During awake period, EEG has fast frequency (15-20 Hz, beta waves), low amplitude (10-30 mV) •When eyes close and relax, (but still awake) EEG now displays higher voltage "alpha waves"-- larger amplitude (9-12 Hz)

Type 1 alcoholics

• Type 1: ~ 75% of alcoholics, males & females • onset occurs after the age of 25. • Psychological dependence, coupled with guilt and fear about alcoholism. • Low degree of alcohol-related fighting and novelty-seeking/high degree of harm avoidance. • Environment plays a key role (triggered by traumatic/ stressful event) -know they have a problem

Type 2 alcoholics

• Type 2: smaller percentage, typically only found in males • Onset occur before the age of 25. • Infrequent guilt/fear about alcohol dependence. • High degree alcohol-related fighting. • Low degree of harm avoidance / high degree of thrill seeking. • Environment plays less of a role -dont think they have a problem -always have a couple drinks in their body -certain personality type

Hallucinogens

• Typically have a low addictive potential • Different types work on different transmitter systems - Mushrooms = Ach - Mescaline = Noradrenaline

Stress definition and steps in the stress response

• Ultimately defined as any change in homeostasis • Typically broken down into three components - Stressful stimulus -->processing/assessment of stimulus--> Stress Response (the body's response to emotionally-charged events) • The "stress response" refers to a number of physiological changes (hormonal, neural, behavioural) that are designed to deal with short-term problems • Acute stress can have beneficial effects - Designed to enhance the "flight or fight" response - Increased energy, metabolism - Enhanced attention, vigilance • However, chronic stress can exert damaging effects on both the body and brain - The most damaging type of stress is unpredictable and/or uncontrollable stress

Epidemiological Factors in Depression/ prevalence

• Unipolar depression typically alternates with normal emotional states, with an episode lasting up to 6-9 months. ― Episodes can recur through life, often increasing in frequency and intensity • Prevalence: In North America, 15-20% of population may be afflicted at any one time - Considerable gender difference: women more likely to be diagnosed - In women, incidence often coincides with major hormonal changes (post partum, menopause) - Incidence of depression has increased over the last 50 years, and age of onset has decreased (currently ~ 27 years old)

Prefrontal Cortex and Planning: Tower of london task

• Used to assess planning of movement sequences • "Move the balls from the start position to this final position in as few moves as possible." • PFC patients need many more moves to reach goal position; often, they don't reach goal at all

Pavlovian (Classical) Conditioning and the classic experiment

• Virtually all animals display Pavlovian conditioning - Helps organism prepare for biologically significant events in response to cues that predict those events • Four main elements - Unconditioned Stimulus (US) = the biologically significant event (meat powder in Pavlov's dog's mouth) a.k.a: primary reinforcer-- has an effect on the body - Unconditioned Response (UR) = normal response to significant event (salivation) - Conditioned Stimulus (CS) = Previously neutral cue that reliably predicts significant event (bell predicts meat powder) - Conditioned Response (CR) = The body's response to the CS alone (salivating to the bell)

general facts on sleeping

• We spend nearly 1/3 of our lives sleeping, suggesting it serves an important function • There are a number of theories as to why we sleep, there is still no consensus (all theories may be accurate in some form)

Obesity: what is it?

• What is it?: Characterized by excessive adipose tissue. • Adult males = >25%, Females = >30% fat content. • 1 in 4 Canadian adults are obese: 1 in 10 Canadian children are obese • Body Mass Index (mass/height squared): Obesity = BMI >30 - (note, this method assumes minimal muscle, so weightlifters (or your professor) shouldn't use this as an estimate.)

Anorexia Nervosa: What is it?

• What is it?: Obsession with body weight/image and food; ~1% of population, mostly women - Characterized by self-induced starvation - Body weight less than 85% expected weight. - Intense fear of gaining weight. - Distorted view of one's body weight or shape. - Many anorexics are obsessed with food, show a higher than normal cephalic phase insulin response- spike in insulin meaning they are likely more hungry, but are often disgusted by a sweet/fatty meal

withdrawal of Psychostimulants (Cocaine, Amphetamines)

• Withdrawal: "the crash" - fatigue, increased appetite, depression, anhedonia, anxiety, irritability, sometimes agitation or extreme suspicion. Also accompanied by increase drug craving. - Withdrawal symptoms tend to be more prominent with amphetamines (particularly methamphetamine) vs cocaine - Many times, withdrawal symptoms are not as visibly apparent at they are for other drugs

Principles of Drug Action: Withdrawal

• Withdrawal: Body's rebound reaction to elimination of drug from system after prolonged exposure. • Typically opposite of the drugs action. - e.g.: after prolonged exposure to sleeping pills, withdrawal causes insomnia • May be viewed as body's attempt to maintain homeostasis. - Drugs cause body/brain to initiate compensatory changes to counteract the effects of the drug (i.e.; tolerance). ‒ When drugs have been eliminated from system, these changes can linger for sometime after = [withdrawal symptoms] -Additional drug taking can alleviate withdrawal •Individuals suffering from withdrawal symptoms are said to be physically dependent: severity of symptoms depends, but usually the longer/greater the exposure = greater withdrawal symptoms.

Prefrontal Cortex and Working Memory

• Working memory = short term manipulation and retrieval of trial unique information - Use info temporarily, manipulate it, then discard it - Info is encoded in one form, but used to guide behaviour in another form - e.g.: remembering a sequence of digits: recalling digits forward = short term memory - BUT - recalling sequence backwards = working memory

REM Sleep and Dreaming

• ~80% of subjects report dreaming when awakened from REM sleep. Only 10% report dreams from SWS awakenings. - Stage 2 awakenings sometimes reveal nonvivid "thinking" dreams • People who claim not to dream report dreaming when awakened during REM sleep. • External stimuli can sometimes influence dreams. - e.g.: spray water on subject in REM sleep, they dream of water falling on them • Dreams run on real time: do not last a few seconds usually. • Sleepwalking and sleeptalking do not occur during REM sleep - Core muscles tend to be totally relaxed.

Stage 2 sleep

•After a few minutes of Stage 1 sleep Stage 2 sets in • EEG looks similar, but additional 12-14 Hz burst of waves called "sleep spindles" are observed. •REMs are rare, EMG low to moderate •This is the period where you don't think you're asleep, but you're not responsive to environment either

Stage one sleep

•After a period, alpha waves decrease, EEG becomes smaller and irregular and slower with random bigger spikes (vertex spike). •REMs are absent, but slow rolling eye movements appear. •The EMG is moderate to low.

Androgenital Syndrome

•Androgenital Syndrome • Caused by congenital adrenal hyperplasia (CAH) - Normally, fetal adrenals produce cortisol, inhibits T release from adrenals - Some fetuses have defect; not enough cortisol produced = MORE THAN NORMAL T • T goes on to masculinize parts of XX fetus - Primordial gonads still form ovaries - Both Wolffian AND Mullerian ducts grow - External genitalia are "intersex"; look like a cross between male and female at birth (can be corrected by surgery) • Gender identity varies; some are raised as girls, but look like boys in puberty and vice versa -look intersex even though they have two X chromosomes

Anorexia Nervosa causes

•Causes: commonly attributed to society's views on female body image. -However, during other time periods, heavier body image was norm, yet women still fasted and starved themselves

Stress and Depression: Cortisol and Diathesis stress model

•Circulating levels of CORT tend to be higher in depressed subjects vs other disorders or controls. - A popular theory of depression is the diathesis- stress model (ie: an individual has some sort of predisposition for depression, and stress can trigger the syndrome)

Prefrontal Cortex and Behavioural Flexibility: Rats in cross maze experiment

•Day 1: rat learns Response Rule (ie: always turn left to get the food) •Visual cue inserted in either left or right arm on each trial; rat must learn to ignore cue •Day 2: rat must now approach Visual Cue •Cue inserted in either left or right arm; rat must stop using old strategy and engage new one •Reversible inactivations of PFC: infuse local anesthetic into PFC; lasts for ~ 1 hr •Inactivate PFC during initial learning: no effect (PFC not involved in learning simple rules) •Inactivate PFC during the shift: MAJOR impairment (PFC selectively involved in switching strategies)

Stress and Depression: HPA axis and cushings syndrome

•Depression has been viewed as a stress related disorder •Bouts of depression can come on during stressful life periods •At least some forms of depression may be linked to alterations in HPA-axis and higher cortisol (CORT) levels •People with Cushing's syndrome have high levels of glucocorticoids and are prone to depression.

•Evidence for estradiol regulation of female rat sexual behavior:

•Evidence for estradiol regulation of female sexual behavior: 1) lesions of VMH or PAG regions disrupt lordosis 2) implantation of estrogens into VMH reinstates lordosis in ovarectomized (ovaries removed) females •This pathway is for particular motor program. Other sexual/maternal behaviours are mediated by other, more complicated brain circuits. •Again, hormones do not cause behaviour, but are necessary for it.

Physiology of Hunger and Satiety: experiment with rats and second stomach

•Experiment: transplant a 2nd stomach in rats, tie it off from rest of intestinal tract •Inject food directly into 2nd stomach, but don't allow it to fully digest •Rats decrease their feeding in proportion to caloric content and volume of food in 2nd stomach •Conclusion: Gut releases hormones (we now call satiety peptides) in bloodstream that stimulate receptors in multiple brain areas to decrease feeding.

What is the function of dopamine?

•Firing of DA neurons is sensitive to cues associated with rewards and absence of expected rewards (aka- reward prediction errors): Dopamine neurons increase firing in response to (as measured by electrode placed in rat/monkey brain): -Unexpected reward--> DA neurons turn on -Pavlovian conditioned cue signals unexpected reward--> DA neurons fire to that cue (not reward itself) Dopamine neurons suppress firing in response to: -omissions of expected rewardss (no delivered reward, no DA firing) --The DA system turns on when something important happens (like unexpected rewards, or cues that predict rewards) -May increase likelihood of approaching reward-related cues or doing actions that led to rewards again

sex as reward in female rats "conditioned place aversion" modification of compartment

•However, if the female was allowed to control the pace of the sexual interaction, THEN she will find it rewarding and display a place preference -female rat can move freely through a barrier put in place in the 'sex compartment' and she darts back and forth but male has collar so he cant fit through the door of the barrier -NOW female finds it rewarding

Arcuate Neural Circuitry and Appetite (long term appetite control) DECREASING APPETITE

•Leptin (activating POMC/CART neurons to dec. appetite through releasing alpha MSH to decrease LH appetite stimulating function) & Insulin (inhibiting effect on AgRP/ NPY neurons that increase appetite) work as long term modulators of appetite •Activate POMC/CART neurons and inhibit AgRP/NPY neurons •POMC/CART neurons inhibit LH via alpha-melanocyte stimulating hormone

hippocampal damage and the type of memory that is impaired

•Medial temporal lobe lesions (primarily the hippocampus) cause a selective deficit in declarative (or explicit) memory, and leave procedural (or implicit) memory intact •Regions such as the striatum (skill/instrumental learning) and amygdala (conditioning) mediate certain types of procedural memory •This is primarily for human memory: animals cannot "declare" what they remember

Current theory of emotion

•Modern theory emphasizes reciprocal interactions with all three factors (physiological arousal, perceptions/ interpretations and thoughts, emotion experience all work in recirpocal interactions) •Accounts for most of experimental data •Original theory by Schachter and Singer said that arousal only adds to intensity of emotion, does not distinguish between emotions •More recent research suggest subtle differences in physiological arousal for emotions like fear and sadness -examples of interaction: arousal can cause subject to look to environment for cues, arousal can trigger emotion, emotion can trigger arousal, emotion effects future interpretation etc.

Hormonal regulation of sexual behaviour: Steroid sex hormones can regulate sexual behaviour in TWO MAIN WAYS

•Organizational Effects: changes in the body/brain that occur during development - These changes are typically permanent - Hormones exert these effects during critical periods of development •Activational effects: effects on body/brain and behaviour that occur after development - Typically occur after sexual maturity (puberty) - These are transient effects, behaviour varies with amount of hormones in blood

Neural Circuits of Emotions: limbic system

•Papez assessed brains of patients w/ emotional disorders and rabid animals •Found consistent patterns of damage in certain areas (Papez's circuit) •Collectively labeled the LIMBIC SYSTEM •In charge of the "four F's" (feeding, fleeing, fighting, sex) •Includes hypothalamus •Three big players: •Amygdala = mediates emotional responses (especially fear); both autonomic and behavioural responses (temporal lobe) •Hippocampus = major memory center (temporal lobe) •Prefrontal cortex = integrates inputs from temporal lobes and other regions to co-ordinate appropriate responses (frontal lobes)

Hormonal Regulation of Male Sex Behaviour: Guinea Pig Experiment

•Rated "sexual activity" of males.- how quickly they engaged in sexual behaviour (classified into studs, slugs, and duds) •Low, Medium and High Groups. •Castrated all males, then monitored sexual activity. •All males THEN receive same large Testosterone injections. •The test dose of T restored all males to PREVIOUS level of sex drive. •Conclusion: OTHER FACTORS control individual differences in sex drive •SOME T is necessary, but more T does not mean more sex drive

5-HT and Acetylcholine Systems and Sleep

•Serotonin (5-HT) released by cells in raphe nucleus. •Projections from raphe can inhibit reticular formation ( decrease wakefullness) •Lesions of raphe = insomnia •However, raphe projects to many other sites throughout brain, including centers which mediate REM sleep •Peribrachial Area: group of nuclei in pons which mediate REM sleep. Use acetylcholine (Ach) as a neurotransmitter • 5-HT from raphe inhibits neurons in this region. increasing 5-HT = decrease REM sleep -the raphe sends some 5HT axons to the reticular formation and seprate group to peribrachial area

stage 3 and 4 sleep

•Stage 3 and 4: High amplitude (>75 mV), slow (0.5-2 Hz) waves called "delta waves" •Stage 4 (aka Stage 3-late) is defined by delta waves at least 50% of the time

Neural Regulation of Male Sex Behaviour in rats

•T is converted to an estrogen in brain, and stimulates mPOA, medial amygdala •Olfactory signals go though medial amygdala, then to mPOA •mPOA sends signals to ventral midbrain and from there, signals go to motor centers and spinal cord -once there is a scent of female in heat, signal is sent to brain, and with regular T levels the brain with be activated (activational effects) and normal mounting behaviour will commence

Neural Regulation of Female rat Sex Behaviour

•The ventromedial hypothalamus (VMH) monitors changes in hormonal levels - Estradiol causes VMH neurons to make progesterone receptors and alters dendrites •When hormones hit peak, activates multisynaptic pathways via periaqueductal gray and medullary reticular formation (motor areas). - Changes in VMH makes these downstream nucleui more excitable •Eventually, signals output through spinal cord, and promote lordosis in response to stimulation. -stimulation on back with primed brain areas= lodrosis

Neural Sexual Development in Primates

•α-Fetoprotien is NOT responsible for protecting primate/human fetus from estrogens •in humans, it does not bind estrogens well •Sex Hormone Binding Globulin (SHBG) protects fetal brain from their own/ moms estrogens •However, unlike rats, early treatment with either estrogens OR androgens by themselves (eg, DHT) can masculinize brain/behaviour in female primates •Rough play, mounting •SHBG will not block some synthetic estrogens, these too can masculinize primate brain, ONLY binds to natural estrogens