Exam 3 Behavioral Neuroscience
glutamate hypothesis of schizophrenia
- deficient activity at glutamate synapses in the frontal cortex accounts for SZ - remember that some postmortem studies show synapse loss in frontal cortex of SZ patients - One link to this idea is the observation that GluR antagonists (PCP, ketamine) have hallucinogenic effects through their blockade of NMDA receptors - In relation to DA, it has been shown that high levels of DA activity in frontal cortex can decrease Glu activity at synapses **can't just administer glutamate because overstimulation of glutamate synapses kills neurons and may cause seizures**
(EEG) electroencephalograph
- device allowed researchers to discover that there are various stages of sleep - EEG uses non invasive electrodes on the scalp to measure brain activity - EEG changes from wake to sleep involve a shift from low amplitude, high frequency waves to a high amplitude, low frequency signal
anterograde amnesia (inability to form new memories)
- dorsal thalamus, mammillary bodies (NA), hippocampus amygdala (HM) play key role in ability to form new memories **The similarity of damage in patients HM and NA indicate that a larger circuit is important in declarative memory than just hippocampus and adjacent cortical fields**
Cushing's disease
- endocrine syndrome where cortisol levels are chronically elevated; these patients show massive hippocampal shrinkage and cell loss (prefrontal has never been examined in Cushing's disease patients)
valproate (for bipolar)
- enhances GABAergic transmission -decrease activity in V-gated Na+ channels, thereby altering (prob. slowing) conduction of action potentials in the brain
NMDA receptors (LTP)
- exhibit a unique voltage-gated property - NMDA receptors are unique from other GluRs as they are permeable to Na+ AND Ca
prosopagnosia
- face blindness; can't recognize faces, including their own - Right, not left hemisphere damage usually leads to impairments in facial recognition
Walter Cannon (general findings)
- first to observe that movements of the digestive organs decreased when animals were aroused -emotional excitement was associated with the following changes: -increase of adrenaline release into the bloodstream -redirection of blood flow from the viscera (internal organs) to skeletal muscles and brain -increased blood pressure and glucose levels
Bipolar I Disorder
- full blown episodes of mania w/ symptoms interfere with everyday life, bouts of depression
Reserpine
- hypertension drug that fueled idea for MAOIs because it caused depressive symptoms -It works by slowing the activity of the nervous system, causing the heartbeat to slow and the blood vessels to relax.
ECT side effects
- impairing short-term memory, and mildly increasing the risk of heart attack - ECT likely increases NTs levels in the brain, esp. monoamines (too much of certain NTs can cause seizures) -May also stimulate growth factors such as BDNF and hippocampal neurogenesis (see later slides)
sensitization
- increase in response to mild stimuli, as a result of previous exposure to more intense stimuli - long-term memory for sensitization involves increases in protein synthesis and new synapse formation
long-term potentiation (LTP) as a mechanism of learning
- is a stable and enduring increase in the activity of synapses that results from a specific type of stimulation - has an early and late phase, the early phase doesn't require protein synthesis, but the late phase does Cellular mechanisms of LTP: -AMPA and NMDA receptors, both are ionotropic GluRs and mediate fast excitatory neurotransmission
Dexamethasone suppression test
- is one test for depression in patients hospitalized for major depression *Dexamethasone is an agonist for cortisol receptors* - If DEX is given to a healthy person, it will suppress the AM rise in cortisol via negative feedback on HPA axis (at the level of the pituitary) - In depressed patients, DEX treatment does not shut off the HPA axis...
response learning
- learning to perform a specific series of movements or responses to your environment - striatum plays key role
Franz and Lashley common ground
- lesion size, not locus, was more important for impacting intellectual function!!
development in schizophrenia
- may aggravate symptoms, but not ultimate cause - viral infection - stress - poor nutrition of mother during pregnancy, nutritional premature birth, low birth weight, complications during delivery
SIDS (sudden infant death syndrome)
- may be due to abnormalities in brainstem circuits that regulate respiration; esp. those involving serotonin -Solution? Leave infant sleeping on back, not stomach
Lithium (used for bipolar)
- mechanism is poorly understood, but has wide-ranging effects - e.g., alters circadian mechanisms, increases BDNF activity - clinically speaking, lithium treats manic episodes, prevents manic relapses, treats depressive stages (esp. decreases incidence of suicide) ***major side effects included though ex vomiting, sleepiness, poor cord., shakiness**
episodic memory (type of declarative memory) *personal facts*
- memory for "temporally dated personal episodes or events - ex. remembering your first day of school - fronto-parietal areas play key role - patient KC showed damage to the frontal parietal areas and showed impaired episodic memory
Bipolar II Disorder
- milder episodes of mania/symptoms, also w/ bouts of depression
split brain patients
- people who have undergone surgery involving transection of the corpus callosum • Split brain patients maintain normal intellect and motivation but they tend to: -Use hands independently in a way others cannot - Respond differently to stimuli presented to only one side of the body
Narcolepsy
- person (or animal) has sudden, intense bouts of sleep during day *Sleep - last 5-30 minutes* - often, narcoleptics suffer cataplexy as well - sudden loss of muscle tone without loss of consciousness (prob. due to aberrant activity in pontine/REM system) - cataplexy in some cases can be caused by strong emotions (positive or negative)
Alpha Waves (EEG) / Stage 1 Sleep
- present when one begins a state of relaxation -Stage 1 sleep is when sleep has just begun - the EEG is dominated by irregular, jagged, low voltage waves - brain activity begins to decline
Consolidation
- putting memories into longer-term storage form; more resistant to disruption or forgetting
semantic memory (type of declarative memory) *general facts*
- recall of general facts, consists of a "mental thesaurus" that provides "the memory necessary for the use of language" - ex knowing the capital of France
MHC (major histocompatibility complex)
- represent a family of genes known to be involved in the immune response to infection - C4 protein : upregulated in SZ patients, and showed that this plays an important role in cortical synapse elimination during development through interaction with microglia
Mania
- restless activity symptoms: - Sustained overactivity - talkativeness - grandiosity - increased energy
somnambulism
- sleep walking; more common among children but can persist into adulthood • Also occurs during SWS; patients are NOT acting out a dream
negative symptoms (schizophrenia)
- social withdrawal - absence of emotionality *negative symptoms remain constant w age*
2 Brain Knife Cut Studies (Bremer 1935)
- suggested that SWS (slow wave sleep) is produced by the forebrain - diagrams on slide 15 week 11
Concept of "Release"
- that focal brain damage decreased some functioning, but in certain instances actually enhanced other functions (Jackson, c. 1890)
Holism
- the idea that the whole is more important than individual parts; very similar in theme to the Gestalt movement - Franz argued injury to only discrete parts of the brain may not damage functions that are the most critical for survival / e.g., if an individual can live with one kidney, then perhaps the same could be true with half a brain
place learning
- the learning of locations or physical positions ex. where we live, where to get food, how to navigate - hippocampus plays key role
Cannon-Bard Theory
- the lower part of the brain, also called the thalamus, controls your experience of emotion - the higher part of the brain, also called the cortex, controls the expression of emotion.
Why isn't all information stored?
- there is likely too much information to store; most of it would probably be irrelevant and unnecessary
declarative memory (long-term)
- things you know that you can tell others - 2 types: episodic & semantic -mammillary bodies & thalamus play key role in declarative memory
nondeclarative/procedural (long term)
- things you know, that you have to show by doing -skill learning, priming, conditioning - ex tying a shoe
Cerveau isolé "isolated forebrain"
- transection of the brainstem at the midbrain produces an isolated forebrain, which exhibits signs of constant SWS - this showed that forebrain system promotes SWS and brainstems provide wakeful and REM sleep - transection through the mesencephalon produces an isolated forebrain ; animal shows constant unresponsiveness and SWS
Encéphale Isolé "isolated brain"
- transection of the lower brainstem produces an isolated brain, which exhibits signs of alternating between wakefulness, SWS, and REM sleep - shows normal responsiveness and sleep-wake patterns -animal with transection at level of medulla; shows normal responsiveness and sleep-wake patterns
3. Pontine System
- triggers REM sleep -Small group of cells in pons, just ventral to locus coeruleus, triggers REM sleep -Some cells project to motoneurons in the spinal cord and strongly inhibit them -this system makes muscles flaccid (i.e., not just relaxed) during REM sleep -YET, pontine neurons also project to forebrain and produce widespread activation ...hence paradoxical EEG pattern during this stage of sleep
Neuroleptics (antipsychotics)
- used to treat schizophrenia - are drugs that block DA receptors - discovered in 1950s
Why do we have multiple stages of memory?
- we can sift information for value and, therefore, store only the most important/ relevant information for longer periods of time
(Begin Emotions and Stress Chapter 15)
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(END CHAPTER 14)
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(REM) rapid eye movement sleep or Paradoxical Sleep
-EEG waves are irregular, low-voltage and fast (i.e., like waking) - Postural muscles of the body are more relaxed than other stages - REM sleep is predominant later in the night - Length of the REM stages increases as the night progresses - REM is strongly associated with dreaming, but people also report dreaming in other stages of sleep
James-Lange Theory
-Sensation triggers bodily changes, which in turn lead to subsequent conscious experiences of these responses: 1. People with a weak autonomic or skeletal response should feel less emotion 2. Increasing one's response should enhance an emotion
deep brain stimulation (DBS)
-approved by the FDA (~10 yrs ago) for treatment of severe depression; involves stimulating ventral portion of medial prefrontal cortex with a surgically implanted electrode -DBS in different brain regions has also been used to treat Tourette's syndrome (i.e., heightened sensitivity to sensory stimuli that is accompanied by the urge to emit verbal tics) --> stimulate the caudate nucleus -major downside is that this requires implantation of an electrode in the brain; this is a very significant procedure that carries a lot of other health risks and complications
SSRIs
-block serotonin (5-HT) reuptake (absorption) back into presynaptic neurons • The term "selective" derives from the fact that these drugs are more preferential to 5HT than other monoamine transporters (milder side effects than tricyclic drugs)
transcranial magnetic stimulation (TMS)
-involves applying a mild magnetic field over the surface of the scalp; this induces an electrical current in a targeted brain region via electromagnetic induction -TMS has been approved by the FDA to treat depression, and several related conditions (e.g., neuropathic pain) -drawback is that TMS can not be well-targeted to deeper-lying brain regions, as these are believed to be most important in mental disorders
concordance rate
-presence of same trait in both members of a family -shown high rate in twins -60% for monozygotic twins; 20% for dizygotic twins -Regardless of whether twins reared apart or together; prevalence is more relative to biological rather than foster parents
LTP late phase (>24hr)
-protein phosphorylation also activates gene expression to make proteins for the cell that strengthens the synapse -one key activated protein that alters gene expression during LTP and learning is CREB (cAMP response element binding) -CREB is phosphorylated during LTP, travels to nucleus, binds DNA promoter regions, and turns on a number of genes
genes in schizophrenia
-schizo is highly heritable, but hard to link with mechanism -variations genes for MHC, DISC1, and COMT genes have been identified
insular cortex
-strongly activated during exposure to stimuli perceived as "disgusting" - this part of cortex is responsible for processing taste information (analogous to A1, V1, and S1)
Donald O. Hebb and the "Hebbian" synapse model
-theory that proposes an explanation for the adaptation of neurons during the process of learning, hypothesizing a basic mechanism for synaptic plasticity -increase in synaptic efficacy arising from a presynaptic cell's repeated and persistent stimulation of the post-synaptic cell "cells that fire together wire together"
LTP early phase (1hr)
-under strong enough stimulation, post synaptic membrane can depolarize enough such that Mg++ becomes dislodged from the channel pore, thereby activating NMDA receptors -NMDA receptors are unique from other GluRs because they are permeable to Na+ and Ca++ -Ca++ influx may initiate signal transduction cascades, induce changes in gene expression and drive protein synthesis related to functional/structural changes to promote long-term synaptic strengthening -retrograde signals (eg NO) can further enhance effect by increasing glutamate release from presynaptic terminal -long-term changes in neuron function may occur in activated synapses following LTP -Ca++ activates protein kinases; enzymes that phosphorylate (add phosphate group to) other proteins --protein phosphorylation is a way of storing energy, tearing off phosphate group from protein at later time releases energy and can be coupled to drive other activities in the neuron --protein kinases activated by LTP: 1. Protein kinase A and C (PKA and PKC) 2. Calcium-calmodulin dependent protein kinase II (CaMKII) PKA, PKC and CaMKII phosphorylate proteins and most importantly, insert AMPA GluRs into the activated synapse -Increasing # of synaptic AMPA GluRs increases the ability of the synapse to respond to future presynaptic stimulation
Sham Rage Experiment
.....when animals that had their cerebral cortices removed.... -resulted in a 5-fold increase in blood glucose levels - increased secretions of the adrenal gland and showed that stimulation of the diencephalon could produce vocalizations, changes in respiration, circulation, piloerection, and coordinated movements ** general idea that emerged from this work is that the diencephalon produces emotional responses but that it is normally inhibited by the cortex **
Major Players in Human Emotion
1) prefrontal regions (i.e., orbitofrontal, cingulate gyrus) 2) amygdala 3) insular cortex
Why do we sleep? (4 reasons)
1. Energy conservation 2. Niche adaptation 3. Body restoration 4. Memory consolidation
4 Major Stages for Sleep/Wake Arousal
1. Forebrain system - that can display SWS by itself 2. Brainstem system - that activates forebrain into wakefulness 3. Pontine system - that triggers REM sleep 4. Hypothalamic system - that affects other three brain systems to determine sleep/wake
4 Dimensions of Emotions
1. Physiological - autonomic, endocrine responses 2. Actions - e.g., laughing; attacking/ fleeing in response to threat 3. Motivation - approach or avoidance behaviors 4. Feelings - subjective experience
Insomnia: 2 Categories
1. Sleep-onset insomnia - often caused by situational factors (shift work, time zone shifts, etc.) 2. Sleep-maintenance insomnia - more due to drugs, psychiatric, neurol. problems -a common cause of the latter is sleep apnea : respiration becomes unreliable and person may stop breathing for a minute -Sleep apnea may may lead to a variety of cardiovascular problems and even neuron death -Continuous positive airwave pressure (CPAP, shown above) machine solves sleep apnea
Stages of Memory
1. acquisition 2. consolidation 3. storage 4. retrieval
Lashley's Laws (1929)
1. equipotentially - all parts of the cortex contribute equally to complex behaviors, such as learning, and one part of the cortex can substitute for any other 2. mass action - the cortex functions as a whole, such that lesion effects on function require sufficiently large portions (i.e., larger lesions = greater deficits)
2 factors of stress appraisal
1. predictability 2. controllability
connectionism
"Simple" functions are subserved by single brain regions/loci; complex functions require multiple loci - more complex processes require more elaborate systems to carry them out. - This may increase selective pressure for hemispheric specialization.
"fast-acting" antidepressants
(N-methyl-D-aspartate receptor) is a glutamate receptor and ion channel found in neurons) -NMDA-R antagonists like ketamine and PCP have very rapid antidepressant effects (within hours) -However the effects also wear off quickly, within 7-10 days
Monoamine hypothesis of depression
(Schildkraut and Kety, 1967) - depression is caused by low 5-HT and NE neurotransmitter activity - based upon the observation that the earliest known antidepressant meds were MAO inhibitors, and the depressive effect produced by reserpine
lobotomy
**frontal lobe lesion surgery** - was supposed to induce relaxation and calmness in individuals with severe or intractable mental disorders - Side effects were not so good - among many, mood swings, change in personality *Walter Freeman is psychiatrist to blame for pushing and performing the lobotomy*
Cortisol
**primary stress hormone** does 4 things in response to environmental threats: 1. Increases blood sugar by activating glucose metabolism 2. Catabolizes fat and proteins (also for energy use) 3. Inhibits immune function, esp. inflammation 4. cognitive adjustments via direct actions in the brain Finally, once the stressor subsides - cortisol "feeds back" onto the brain to shut off HPA axis response or : "glucocorticoid-mediated negative feedback" of the HPA axis
Adrenocorticotropic hormone (ACTH)
*Cells in the anterior pituitary synthesize and secrete this into bloodstream* - stimulates the release of cortisol from the adrenal cortex; cortisol is a glucocorticoid hormone that broadly affects the body and brain
positive symptoms (schizophrenia)
*any change in behaviour or thoughts* - paranoia - delusions - structured hallucinations *Aging is associated with the decline of positive*
general adaption syndrome
*connection between between stress and disease* 1. Alarm reaction - initial response to stress 2. Adaptation stage - includes activation of appropriate response systems and re-establishment of homeostatic balance 3. Exhaustion stage - occurs when stress is prolonged or severe; characterized by increased susceptibility to disease
Genetic Basis for Depression
*no single gene* - One gene that has received a lot of attention is the 5HTT-LPR (serotonin transporter-linked polymorphic region) - individuals with the short form of this gene have an increased likelihood of MDD, anxiety disorders, or PTSD (remember comorbidity of these disorders) - having said this, stress is a huge predisposer - people with high levels of circulating cortisol are prone to MDD
1. Forebrain System
*remember from Bremer's work that this, when isolated, may produce SWS on its own* -stimulation of the preoptic area (POA) produces sleepiness, whereas lesions produce insomnia -Basal forebrain POA neurons become active at onset of sleep and release GABA at a key hypothalamic structure, the tuberomammillary nucleus : that is important for increasing arousal
Causes of the Depression
*still poorly understood, although a pervasive idea is that depression results from dysfunction of the brain serotonergic system* Some proposed causes: -genetic predisposition involving altered SERT activity -synapse loss in prefrontal cortex, esp. as caused by stress -low levels of hippocampal neurogenesis -low levels of brain neurotrophins ( SSRIs may act on one or several of these processes )
plasticity of memory
- "changeability" of neurons; not just functional, but structural modifications underlie learning and memory
Mental Illness in US
- 1/3 of population report symptoms at some time in their life that match features of major psychiatric disorders - Rates between men and women are similar, although depression is more prevalent in women, and drug/alcohol dependence is prevalent in men
Sleep Spindles (EEG) / Stage 2 Sleep
- 12-14 Hz waves during a burst that lasts at least half a second - K-complex : a sharp high-amplitude negative wave followed by a smaller, slower positive wave
Depression Treatment
- 50% of people taking antidepressants get better - 50% of people undergoing therapy get better - 30% of people taking placebos get better - Combining treatments produces little to no increased effect - Little difference regarding the various types of antidepressants (see below)
hemispheric activity
- The left hemisphere is dominant for speech in 95% of right-handed people - Language dominance for left-handers is a bit different: 19% have right hemispheric dominance 18% have bilateral language functions
psychosocial dwarfism
•Growth failure that results from psychological and social factors mediated through CNS and its control over endocrine functions (Green et al., 1984) • When such children are removed from stressful circumstances, many begin to grow rapidly (asterisks) • Prolonged cortisol from HPA hyperactivity secretion may inhibit growth hormone (GH) release, which is necessary for physical development and growth in children
paraventricular nucleus of hypothalamus
Final common pathway in the brain for activation of HPA axis
Bipolar Disorder vs Schizophrenia
SIMILARITIES TO SZ: • Late adolescence/ teen onset • Genetics are complicated, BD is not one, but probably many disorders • Brain abnormalities in BD are similar to schizophrenia, i.e., more than depression (hence the name change away from "manic depression") • Family history of SZ is common in BD patients • Cognitive symptoms in mania overlap with some positive symptoms in schizophrenia DIFFERENCES: • antipsychotics don't work as well in BD, but are used sometimes in instances where more SZ-like symptoms are present • Lithium works well to treat BD but not SZ...
3.) MOTIVATION
approach or avoidance behaviors
1.) PHYSIOLOGICAL
autonomic, endocrine responses ------
arcuate fasciculus
axon fiber pathway that connects Broca's (speech prod.) and Wernicke's (speech compr.) areas
MAOIs (monoamine oxidase inhibitors)
block MAO activity, and thus prevents the breakdown of monoamine NTs (DA, NE, 5-HT) **Iproniazid is an example of an MAO inhibitor that used to be used a lot**
stress
body's multisystem response to any challenge that overwhelms, or is judged to overwhelm, selective homeostatic response mechanisms **stress in't always bad**
left hemisphere
controls language, math, and logic, visual patterns
disgust
cortical localization seems to be evident for one emotion, disgust.
long-term memory
declarative and nondeclarative (procedural)
habituate
decline more rapidly, become used to (this happens to HPA responses)
reactive depression
due to an adverse life event; contrasted from normal grieving; usually resolves within 6 months with therapy/ meds
double dissociation
essentially exclusive
MDD (major depressive disorder)
extreme feelings of sadness and helplessness everyday for weeks on end •may Include (although does not require all) the following characteristics (DSM-IV): - Lack of energy - Feelings of worthlessness - Suicidal thoughts - Feelings of hopelessness - Disrupted sleep patterns - Difficulty concentrating - Loss of pleasure
Bupropion (atypical antidepressant)
family of drugs with different pharmacology than tricyclics or SSRIs that also act as antidepressants -Bupropion inhibits reuptake of DA and NE but not 5-HT
Grid cells in entorhinal cortex
fires at regular intervals as an animal navigates an open area, allowing it to understand its position in space by storing and integrating information about location, distance, and direction.
Lateralization
idea that each hemisphere of the brain is specialized for different functions
long exposures to cortisol
in rats have been shown shrivel pyramidal neurons and destroy excitatory synapses in the hippocampus and prefrontal cortex
2.) ACTIONS
laughing; attacking/ fleeing in response to threat ----- -Brain systems of avoidance behaviors - Pavlovian classical conditioning commonly used to study this
delta waves
long, slow waves that indicate the deepest stage of sleep
retrograde amnesia
loss of memories from our past, inability to retrieve past memories
PTSD
occurs in some people after certain crises or terrifying experiences symptoms: - Frequent distressing recollections - Nightmares - Avoidance of reminders of the event - Exaggerated arousal in response to noises and other stimuli
serial position effect
our tendency to recall best the last and first items in a list
James Papez (Papez circuit)
outlined a circuit to account for emotion, and involved new regions not previously considered as being important for emotion: Hippocampus, cingulate gyrus, anterior thalamic nuclei (limbic system)
Corticotropin-releasing factor (CRF)
peptide synthesized and secreted by neurons in the PVH A subpopulation of neurons release CRF into the anterior pituitary portal system
Engram
physical representation of what has been learned
posterior hypothalamus
plays an important role in the expression of emotions
MAO (monoamine oxidase)
presynaptic enzyme that degrades neurotransmitters into metabolites
confabulate
relating to memory : provide a narrative of events that never happened, or when trying to recall information will fill in details of a story with fictitious information
temporal
relating to time
Amygdala
required in fear conditioning, mediator for fear response. parts involved include: lateral nucleus of amygdala, basal lateral nucleus, central amygdala. (slide 33, week 12)
limbic system
responsible for much of emotion
Temporal Division of Memory
senses --> sensory buffer --> working/short term memory --> long-term memory
major depressive disorder
severe, prolonged depression; may be precipitated by trauma, but not necessarily
right hemisphere
spatial perception, visual recognition, emotion
4.) Feelings/Emotions
subjective experience • Emotions tend not to be localized in distinct parts of the cortex• A single type of emotion increases activity in various parts of the brain but not in one single region...
Comorbidity
the co-occurrence of two or more mental disorders in a single individual
sympathetic nervous system
the division of the autonomic nervous system that arouses the body, mobilizing its energy in stressful situations (ie. for fight or flight)
James' Lasting Contribution (after his theory was proven wrong by physiologists)
the experience of emotions involves a component of "reading" of the state of one's own body
brain self-stimulation
the process in which animals will work to provide electrical stimulation to particular brain sites, presumably because the experience is very rewarding
alpha waves
the relatively slow, short brain waves of a relaxed, awake state
psychosurgery
the use of surgical manipulation to treat severe mental illness (1940s)
electroconvulsive therapy (ECT) for MDD
treatment option for major depressive disorder -electrical current is passed through the brain induced in patients under anesthesia and it produces mild seizure like activity - used for highly suicidal patients and produces immediate antidepressant response in ~50% that lasts for at least several months
corpus collosum
used by the left and right hemisphere to readily exchange information primarily through axonal fibers **Other areas that exchange information include: - The anterior commissure - The hippocampal commissure
Modafinil (Provigil)
used for narcolepsy / cataplexy, other treatments include amphetamines
How do antidepressants work?
• Alteration of synaptic activity produced by antidepressants is rapid - occurs within hours • However, signs of recovery from depression are not evident until weeks later • Some depressed patients show normal or even increased levels of serotonin turnover in blood samples; although assay of NTs in the blood or cerebrospinal fluid is not a reliable predictor of brain levels of NTs
Tryclics
• Blocks transporter proteins that reabsorb 5-HT, NE, and DA back into presynaptic terminal • Effect is lingering increases in monoamine NT levels in synaptic cleft • This is thought to results in an increased stimulation of postsynaptic neurons Side effects:- Blocks histamine receptors: drowsiness - Blocks acetylcholine receptors: dry mouth, difficulty urinating (muscle problems), decreased sex drive - Blocks peripheral sodium channels: heart irregularities
summary of potential mechanisms underlying depression
• Dysfunction of the brain 5-HT system • Stress and/or elevated cortisol results in overactivity of the HPA axis • Synapse loss in the prefrontal cortex • Decreased hippocampal neurogenesis in the dentate gyrus • Low levels of neurotrophins in cortex and hippocampus, esp. of BDNF COMBINE WITH: "big" environmental experiences such as trauma or early life stress
Antidepressant Drugs
• MAOIs (Monoamine Oxidase inhibitors) • Tricyclics • SSRIs (Selective serotonin reuptake inhibitors) • Atypicial antidepressants - differential selectivity for DA and NE reuptake instead of preference to 5HT
Narcolepsy Contd.
• Narcoleptics typically enter REM immediately upon falling asleep rather than SWS at night • Narcoleptic dogs - also show immediate entry into REM sleep • Mice with the hypocretin/ orexin gene knocked out also show narcolepsy • humans with narcolepsy have also been shown to have profound loss of hypocretin neurons (located in tuberomammillary and lateral hypothalamic regions), prob due to degeneration
REM behavior disorder (RBD)
• Patients appear to be acting out a dream, of somewhat organized-seeming behavior • Begins around age 50 and more common among men • Onset often followed by Parkinsons or dementia
Summary of Cellular Mechanisms of Learning
• Plasticity is the key term used to described synaptic strengthening that underlies the formation of new memories in the brain • This plasticity may be functional (i.e., more transmitter released, increased number of GluRs) or structural (more synapses, more neurons in dentate gyrus) • Remember that plasticity should only be occurring in brain regions essential for the storage of the particular type of memory involved (e.g., hippocampus declarative/ spatial memory)
1. energy conservation
• Reduced body temp, slower respiration, slower heart rate --> reduced metabolic activity • YET, sleep reduces metabolic rate by only 5-10%
How are memories selected for long term storage?
• Rehearsal - simply going over information multiple times - massed vs. spaced training • Connecting with old information • Emotional arousal
3. Body Restoration
• Sleep helps rebuild/restore body materials and functions • Prolonged deprivation --> weakened immune system • Work at night vs. day --> increased risk of cancer • Does not refer to simple wear and tear --> e.g. exercise does not cause people to sleep longer
medial forebrain bundle
• This pathway contains dopamine neurons, arising from the ventral tegmental area (VTA) that innervate the nucleus accumbens (recall mesolimbic system) • Pleasurable experiences, or emotions pertaining to joy, happiness, all involve activation of the dopamine-nucleus accumbens pathway • More recently, evidence suggests that VTA-DA neurons play a role in predicting reward- and aversive-related cues
Robert Sapolsky (2001) Baboon Study
• This troupe has an abundance of food, and no predators, yet, animals show a considerable amount of stress • Vigorous competition surrounds courtship, and establishment of dominance hierarchies • Stress physiology (i.e., cortisol and epinephrine levels) is largely influenced by status in hierarchy ( i.e., alpha = lower stress hormones) ***A key finding of these studies is that cortisol levels remain high in chronically stressed monkeys***
C4 Knockout in mice
- C4 protein in mice leads to less synaptic elimination (i.e., more overall synapses) during cortical development - therefore, synapse loss in SZ may result from higher levels of C4 expression due to an allelic variation in this gene -
Where are memories stored?
- Explicit memories - (episodic), (semantic) there are three important areas of the brain: the hippocampus, the neocortex and the amygdala - Implicit memories, such as motor memories: the basal ganglia and cerebellum.
hippocampal neurogenesis (as a mechanism of learning)
- Neurogenesis is another potential mechanism of learning - Precursor cells in the dentate gyrus are constantly undergoing cell division, some live and some die - The ones that survive differentiate into adult granule neurons and become integrated in the granule cell layer in this region **learning enhances the survival of these neurons**
Walter Cannon (viscera findings)
- Cannon recognized that cutting the nervous system projections from the viscera to the brain in cats did not prevent the expression of emotional responses indicative of anger, disgust, fear, etc -He also appreciated that visceral responses were sometimes slower to appear than conscious emotional states that they were supposed to trigger - Also - the visceral responses evoked by different emotions were the same regardless of emotional state
Criticisms of James-Lange Theory
- Charles Dana (1921) reported a patient that fell off of a horse and broke her neck at C3-C4 of spinal cord, and lost all cutaneous and deep sensation from the neck down, yet they still showed all of the ranges of emotion - There is a neurological condition known as "pure autonomic failure" , yet these people still report feeling emotion -This suggests that other factors are involved in the perception of emotion
4. Memory Consolidation
- Considerable evidence in recent years indicates that sleep PROMOTES memory consolidation: • Evidence suggests that SWS helps in the consolidation of declarative memories • and involvement of REM sleep in consolidation of procedural memories
Structures for Different Aspects of Fear Responses
- Defensive behaviors =(periaqueductal gray; "central gray" on diagram) -Autonomic activation = (through Lat. Hyp.) - Stress hormone responses = (through bed nucleus of the stria terminalis and paraventricular hypothalamus; BST and PVH)
Slow Wave Sleep, Delta Waves (EEG) / Stage 3, Stage 4 Sleep
- EEG recording of slow, large amplitude delta waves - Slowing of heart rate, breathing rate, and brain activity - Highly synchronized neuronal activity -predominate early in the night - The length of stages 3 and 4 decrease as the night progresses
2. Niche Adaptation
- Sleep enforces adaptation to a particular ecological niche - For example, if the animal is better at gathering food during day/night, or may avoid predators day/night, then selective pressure may have favored sleeping in the other part of day
hippocampal neurogenesis
- Some have argued that low levels of neurogenesis in the dentate gyrus of the hippocampus may underlie depression - SSRIs have been shown to robustly increase levels of neurogenesis
non-REM (NREM) sleep
- Stages other than REM -When one falls asleep, they progress through stages 1, 2, 3, and 4 in sequential order - After about an hour, the person begins to cycle back through the stages from stage 4 to stages 3 and 2 and than REM - The sequence repeats with each cycle lasting approximately 90 minutes
Synapse Loss in Prefrontal Cortex
- Stress or high levels of cortisol can lead to synapse loss in prefrontal cortex - prefrontal dysfunction is thought to be important in depression because of its role in regulating cognitive and affective information processing **ketamine used in rodents was shown to act on these pathways to restore synapses in prefrontal cortex**
Habituation
- decrease in response to a stimulus that is presented repeatedly
brain abnormalities in schizophrenia
- decreased frontal cortex activity during memory tasks - ventricular enlargement; -some postmortem studies show synapse loss in frontal cortex
Amygdala is activated under wide variety of emotional contexts...
- Threatening faces- Frightening situations - Viewing visually disturbing scenes - Viewing people of other races/ nationalities (i.e., that they are hostile toward or fear) - Under a variety of anxiety like conditions (in disorder and normal subjects)
Why isn't information immediately put into long-term storage?
- achieving long-term/ permanent storage requires processes in the brain that are more effortful and take longer
2. Brain Stem
- activates forebrain into wakefulness -Reticular formation : collection of cells throughout brain stem; many of which are cholinergic (ACh) -ACh neurons project to variety of structures in brain to promote wakefulness -locus coeruleus : major source of NE for entire forebrain; has stimulatory effects on alertness
4. Hypothalamic System
- acts as a counter-weight to the other three brain regions, sends axons to the other 3 sleep centers and coordinates them, enforcing patterns of sleep -Lateral hypothalamus and tuberomammillary nucleus of the hypothalamus - utilize a peptide transmitter: hypocretin/ orexin Hypocretin/ orexin: have stimulatory effects on arousal, but their role is more nuanced, since they provide a counter-weight to the other systems to ensure a smooth transition across both sleep and waking states *problems with loss of hypocretin-orexin can lead to disorganized sleep, such as REM like lack of muscle tone while awake (narcolepsy)
Memory
- an experientially induced change in the nervous system that may be expressed in future behaviors
mood stabilizers (used for bipolar)
- are used more frequently today and work better (or at least they have less dangerous side-effects), e.g., valproate, carbamazepine -decrease activity in V-gated Na+ channels, thereby altering (prob. slowing) conduction of action potentials in the brain
planum temporale
- area of the temporal cortex that contains Wernicke's area, and is substantially larger in the left hemisphere in 65% of people **MRI studies indicate that this difference is related to language lateralization**
Treatments for Insomnia
- barbiturates; benzodiazepines (highly addictive) - For sleep problems, the best approach is to develop a regular routine to exploit the body's circadian clock (Webb, 1992) - go to bed in the evening when you feel sleepy-have a bedtime routine (e.g., dark, quiet environment)-ignore preconceived notions about how much sleep you "need"
atypical antipsychotics (neuroleptics)
- block D2 but have other effects less well understood - prob some 5-HT receptor antagonism / e.g., amilsulpiride, clozapine)
typical antipsychotics (neuroleptics)
- block D2 receptors (e.g., chlorpromazine)
epigenetic changes
- can result from early life stress, and effect stress reactivity during adulthood - Early life trauma in humans is also associated with a greater risk of major depressive disorder later in life and is now thought to have an epigenetic basis
Ascending reticular activating system (ARAS)
- collection of anatomical structures with different functions, but there are "wake-maintaining circuits in this region
Bipolar
- cycles between two extremes, generally mania and depression
Unipolar
- cycling between being feeling normal and depressed
place cells / CA1 (in hippocampus)
Types of cells found in Hippocampus whose activity becomes associated with particular parts of familiarizing an environment **hippocampus plays significant role in spatial learning**
falling asleep waves
amplitude increases, frequency decreases
STRESS
CH 15
entorhinal cortex
an area of the medial temporal cortex that is a major source of neural signals to the hippocampus
anterograde amnesia
an inability to form new memories
Walter Hess
Hess found that stimulating the posterior hypothalamus in cats (while awake) produced hissing and spitting, piloerection, pupillary dilation, ears moving back .....they all ceased when the stimulation ended
Pathways to PVH (category specific)
Physiological stress - brain stem projs. to PVH; mostly from nucleus of solitary tract and ventrolateral medulla e.g., blood loss, low oxygen, infection,• Psychological stress - pathways are more sensory; relayed to limbic regions and then to PVH via indirect pathways --> Primary relays are bed nuclei of the stria terminalis (BST), dorsomedial and posterior hypothalamus e.g., predator exposure, psychosocial
Cortisol Mediates
Short Term Adaptation: -mobilization of energy reserves -increased cardiovascular output -suppression of digestion -suppression of growth -suppression of reproduction -altered immune function -heightened awareness, cognition Long Term Pathology: -fatigue, type 2 diabetes myopathy, -hypertension -ulcers, irritable bowel disorder -psychosocial dwarfism -amennorrhea, impotency, loss of libido -immunosuppression, risk of infection -Synaptic pruning (i.e., cortex, (i.e., cortex, hippo.)
2 Parts of Stress Response
Stress activates two physiological systems in the body: 1. The sympathetic nervous system - "fight or flight" response that prepares the body for brief emergency responses 2. Hypothalamo-pituitary-adrenal (HPA) axis - produces endocrine changes to enable adaptation; complements sympathetic response (HPA axis activation predominates during prolonged stressors; we have already talked a lot about the sympathetic response, so we will focus on the HPA axis) (HPA axis activation is initiated when afferent information enters into the brain, and is ultimately conveyed to the paraventricular nucleus of the hypothalamus (PVH) )
fight or flight response
activation of the sympathetic division of the autonomic nervous system, allowing access to energy reserves and heightened sensory capacity so that we might fight off a given threat or run away to safety