QUIZ 3

causes of schizophrenia: initially seen as disorder of "nurture"

-"bad parenting" (especially mothers) blamed -revised by Irving Gottesman's twin studies -identified strong genetic component to schizophrenia

biological understanding of mental illness

-"general paresis of the insane": mania, delusions, cognitive decline -initially blamed on psychological factors, but caused by syphilis and eradicated by penicillin -other examples of mental illness with known biological basis: -niacin deficiency - agitation, impaired reasoning, depression -HIV - dementia -some cases of OCD linked to strep infections

better face recognition: super recognizers

-1-2% of population -remember 80% faces they seen (usual: 20%)

Alzheimer's disease (AD)

-1/20 people by age 65, >1/2 people over 85 -2/3 women (women live longer) symptom onset typically after 65 -mild cognitive impairment (MCI): memory loss (episodic, proper names), transient confusion, restlessness, word finding difficulty spatial disorientation, problem solving and planning challenges -dementia: deterioration of memory and communication, disorientation, confusion, behavioral changes, difficulty completing familiar tasks, depression, inability to recognize family members -final stages: difficulty speaking, swallowing, walking -progression of MCI -> dementia may take years -risk factors -age: over 65, family history -APOE e4 allele (40-65% people diagnosed have at least one copy) -cardiovascular disease: smoking, obesity, diabetes, high cholesterol, hypertension (in midlife for many of these factors) -traumatic brain injury -less education, less social/cognitive engagement

SLEEP!

-1/3 of our lives -limited control -universal among higher vertebrates, maybe even all animals -reversible, reduced responsiveness to environment

language acquisition: similar in all cultures

-6 months: babbling -18 months: understand about 150 words, speak about 50 -1-2 years: mother tongue (motherese - exaggerated, slower, clearer vowels) -3 years: about 1000 words -statistical learning: some sound combinations more likely than others

orexin (hypocretin, HCRT) - producing neurons and narcolepsy

-70,000 neurons -cell bodies in lateral hypothalamus -inhibits REM -project to neurons involved in feeding, sleep-wake, neuroendocrine homeostasis, autonomic function -patients with narcolepsy lose >90% HCRT-producing neurons

sleep cycle - patterns of REM and non-REM sleep

-75% non-REM, 25% REM -cycle repeats about every 90 minutes 1: non-REM (minutes, light sleep, rolling eye movements) 2: 5-15 minutes, sleep spindles 3: slow delta rhythms, few movements 4: 20-40 min, deepest, large <2 Hz rhythms 3, 2 (10-15 minutes) REM: fast EEG beta/gamma rhythms, eye movements -as sleep goes on, more REM

genetic and environmental contributions to narcolepsy

-98% patients are HLA-DQ*0602 haplotype theory: perhaps it presents autoantigen to CD4+ T cells -> autoimmunity -monozygotic twin concordance only 25% (environment causes it) -perhaps linked to flu pandemic/vaccines, suggesting a viral antigen involved

slide 26: amyloid precursor protein (APP) can be cleaved to form AB or P3

-AB is linked to Alzheimer's -a-secretase cleavage prevents AB formation -Y-secretase cleavage site variable -a-secretase is normal, keeps AB from forming -B-secretase, and then Y-secreatse - forms AB

progression of AD

-AB plaques first mark disease, followed by tau aggregates, then symptoms -changes in memory, brain structure, and clinical function

anterior pituitary (gland, not brain): source of the endocrine hormones

-ACTH -FSH/LH (ovulation/spermatogenesis) -TSH (thyroid - metabolism) -GH (cell growth/regeneration) -prolactin (lactation)

AB formed by breakdown of APP

-APP conserved across species, AB subregion not conserved -amyloid accumulates with age in many mammals -no tangles, neurodegeneration, dementia -APP found at synapses, normal function unknown -disease could be due to loss or gain of function

AB plaques formed by breakdown of amyloid precursor protein (APP)

-APP expressed in many cell types -cleaved by B-secretase -80-90% makes: AB40 -some of it makes AB42: hydrophobic, aggregates -soluble AB42 levels correlate with synapse loss

Down's syndrome and amyloid hypothesis

-APP on chromosome 21 -Trisomy 21 (Down's) >50% develop AD -AD like plaques in 30s-40s, dementia in 50s -it seems that 3 copies pushes progression of the disorder

current therapeutic approaches for AD

-B, Y-secretase inhibitors -aggregation blockers -chelation therapy (reduces AB plaques) -NMDAR blockers -immunotherapeutics

synaptic homeostasis: metaplasticity (slow)

-BCM model: modification threshold adjusts depending on postsynaptic activity -too little activity, shifts left so easier to get LTP -too much activity, shifts right so harder to get LTP -point where modification switches from LTD to LTP is modification threshold

language processing: Wernicke-Geschwind model

-Broca's, Wernicke's, arcuate fasciculus, angular gyrus -pathway for repeating a spoken word: auditory cortex, Wernicke's, arcuate fasciculus, Broca's, motor cortex -pathway for repeating a written word: visual cortex, angular gyrus, Wernicke's area, arcuate fasciculus, Broca's area, motor cortex

2 left hemisphere areas affect language, but in different ways

-Broca's: producing speech -impairment: anomia -overpracticed speech preserved -function words omitted (be, or), but nouns like bee or oar are okay -excellent comprehension -Wernicke's: comprehending speech -impairment: Wernicke's aphasia -fluent speech, poor comprehension -clarity/gibberish, can't follow spoken/written directions -musical gibberish

the impact of sport injuries

-CTE: neurogenerative disease after repeated head injuries (contact sports, domestic violence, military) -form of tauopathy (like Alzheimer's) -symptoms appear 8-10 years after injuries -ADHD, headaches, confusion, disorientation; memory loss, impulsive behavior; dementia, movement disorders, depression/suicidality -can be diagnosed only after death: brain atrophy, enlarged ventricles, tau tangles -largest demographic - contact-sport athletes -football, ice hockey, rugby, boxing (punch drunk), soccer (headers), wrestling -linked to suicides of former NFL players

BUT there's more to schizophrenia than DA

-D2 receptor antagonists don't treat negative symptoms -atypical antipsychotics don't affect D2Rs, maybe serotonin? -structural abnormalities, including thinning of specific areas of cortex, and changes in inhibitory neurons

dopaminergic system

-DA: metabolic precursor to NE -function: motivation, reinforcement, reward, initiation of movement -disease: Parkinson's

treatment of mood disorders

-ECT (artificially induced seizures) -works rapidly (reduce suicide risk) -may act via hippocampus -temporary effects on memory -psychotherapy -antidepressant medications: -MAO inhibitors: prevent degradation of catecholamines -tricyclics -SSRIs -require weeks to become effective -suggest long-term adaptive changes rather than direct effects on neurotransmission

monitoring neuronal population activity: electroencephalogram (EEG)

-EEG scalp electrodes measure voltage generated by current flow during excitation of thousands of pyramidal neuron dendrites in cerebral cortex -we CANNOT measure activity of one neuron via EEG

different body functions in REM vs non-REM sleep

-EEG: awake: low voltage, fast non-REM: high voltage, slow REM: low voltage, fast REM: -hallucinating brain in paralyzed body -EEG looks like waking (paradoxical sleep) -atonia of skeletal muscle EXCEPT respiratory, eyes, inner ear -high sympathetic ANS, temp control off, temp drifts down -heart and respiration increase but irregular non-REM: -idling brain in moveable body -low muscle tension/movement, low temp, low energy consumption -high parasympathetic ANS, low heart rate, respiration, kidney function; high digestion -low brain firing rates

LTP in hippocampus induced by high frequency stimulation of presynaptic axons

-Hebbian strengthening -but doesn't pre and post have to fire together?

disorders of procedural memory

-Huntington's: damage to striatum, uncontrollable movements, difficulty learning to associate stimuli with a motor response -Parkinson's: damage to SnR, which projects to striatum, difficulty initiating movement and difficulty learning "forecasting" task

origins of vaccines

-Jenner: milkmaids with cowpox were immune to smallpox -hypothesis: cowpox pustules confer protection against smallpox? -Pasteur: chickens and cholera - previous exposure confers immunity, attenuated (weakened) exposure works

further evidence for role of hypothalamus in memory

-Korsakoff's syndrome -chronic alcoholism leads to a thiamin deficiency -damages dorsomedial thalamus -anterograde (consolidation impaired) and retrograde (recall impaired) amnesia

hallucinogens that target modulatory systems

-LSD, mushrooms, peyote (dreamlike state, heightened sensation, synesthesia) -active components - serotonin receptor agonists (mimics) -inhibit serotonergic outflow from raphe (also seen in dream-sleep, but block isn't necessary or sufficient)

cooperativity

-LTP induced by pairing pre and post depolarization (Hebbian) -individual weak inputs that coincide can be strengthened, if, together they fire a postsynaptic neuron

the glutamate hypofunction hypothesis

-NMDA receptor antagonists PCP, ketamine -recapitulate positive and negative symptoms of schizophrenia -no effect on dopamine -NMDAR-deficient mice have schizophrenia-like behaviors -strongest genetic linkage to schizophrenia: MHCI immune proteins -MHCI directly inhibits NMDARs

How does coincident firing strengthen synaptic communications?

-NMDA receptors (molecular coincidence detectors) -to flux Ca+, NMDARs require coincident: 1. presynaptic depolarize (release glutamate) 2. postsynaptic depolarization (removes voltage-dependent Mg2+ block)

mechanisms of LTD at CA1 synapses

-NMDAR dependent -requires Ca2+, but less over longer time -activates phosphatases (not kinases) -AMPA receptors dephosphorylated, removed from synapse -NMDAR independent (requires mGluRs)

mechanisms of metaplasticity: changes in NMDAR subunit composition (slow)

-NMDAR subunits -NR2B fluxes more Ca2+, favors LTP -NR2A fluxes less Ca2+, favores LTD -after high activity, more NR2A (LTD) -after low activity, more NR2B (LTP)

synaptic homeostasis: synaptic scaling (slow)

-NT release blocked, increased sensitivity to NT -inhibition blocked, reduced sensitivity to NT -sensitivity of all synapses onto that postsynaptic cell multiplied or divided by the same factor -restores normal firing levels in postsynaptic neuron -maintains relative differences in strength of different synapses = information -involves Ca2+ influx into soma, CaMKIV, new gene expression

Oxytocin, vasopressin, and pair bonding

-Prairie voles are monogamous, high levels of vasopressin and receptor. -block vasopressin, they become meadow voles: promiscuous, low levels of vasopressin and receptor. Add it, they go back to being prairie voles. -receptor levels variable among individuals but correlate with behavior -receptor gene variants differ in bonding vs nonbonding species -oxytocin receptor expression more dense in reward system of prairie voles

EEG: different cortical rhythms in REM vs non-REM sleep

-REM - more awake-like EEG -non-REM - slow wave sleep

syndromic autism: conditions sharing symptomatic overlap with autism

-Rett syndrome (defects in MeCP2) -mostly seen in girls bc they live to be diagnosed -develop normally for 6-18 months, development slows, stops, regresses -social withdrawal, loss of language, motor symptoms (hand wringing)

biological clock is in the SCN of the hypothalamus

-SCN lesions disrupt circadian rhythms -is rhythm generated in SCN? -SCN cells in dish maintain electrical activity synchronized to previous light cycle -transplants: hamsters with SCN lesions received transplants, circadian rhythms restored and match rhythm of donor -no SCN, no rhythm -someone else's SCN, their rhythm -SCN entrained by light

bilateral brain activation during language tasks

-Wada procedure: left hemisphere is dominant for language -imaging: right is also very active

Do vaccines cause autism?

-Wakefield paper that suggested link was deeply flawed -follow-ups: epidemiology to date does not support link -introduction of MMR doesn't coincide with rise of autism -thimerosal removed in vaccines, rise still happened

neurology of alcoholism

-Wernicke's encephalopathy -eye movement abnormalities, global confusion, ataxia, death -Wernicke-Korsakoff psychosis (anterograde amnesia and personality changes) due to vitamin B deficiency

Where do synchronous rhythms come from?

-a central pacemaker -mutual excitation/inhibition

HM's ability to form some types of memories was still intact: ex - motor learning

-able to learn motor skill - procedural memory -also able to briefly remember lists of numbers - working memory

slide 27: AB peptide production

-abnormal cleavage of amyloid precursor protein leading to excess amyloid accumulation

activation in human PFC during working memory tasks

-activity during the delay -different areas for identity, location of face -cortical areas outside frontal lobe also appear to fire during working memory (ex: LIP, lateral intraparietal cortex, guides eye movements)

VTA-Nac forebrain circuit serves hedonic reward (pleasure) or drives to seek it?

-addictive substances all act on this pathway, despite targeting different NTs (heroin: opiate, nicotine: cholinergic, cocaine: dopaminergic and noradrenergic) -destroy DA axons in lateral hypothalamus (eating stops - do not want), lacks motivation to seek food -fails to reduce hedonic response to food on tongue (still likes it) -stimulate same axons: produces craving (want), no change in hedonic impact (like) -circuit may actually control drive to SEEK pleasure, not reward itself

vaccinations have (rare) serious side-effects

-adverse reactions expected in small number of people for most mdical treatments

two classes of affective and mood disorders

-affect: emotional state or mood bipolar disorder -mood swings from manic state (grandiose, energetic, sleepless, talkative, racing thoughts, distractible, impaired judgement) to depressive (feeling worthless and empty) -Type I: just manic/manic depressive -Type II: hypomania (not as severe) and major depression, overall milder and has increased efficiency, accomplishment, creativity major depression -women twice as often -only depressive phase of bipolar disorder -daily, for months: lowered mood, anhedonia daily, appetite/sleep changes, guilt, reduced concentration, thoughts of death

cellular response to injury in CNS

-after injury at some site, there's breakdown of oligodendrocytes (myelin insulation) -whole neurite starts to degenerate -recruitment of immune cells, called astrocytes, and you end up with loss of neurite/whole neuron

SSRI's

-allow serotonin to be active in the synapse longer -typically take 2-4 weeks to be effective -hints at longer term effects

PET scan to visualize AB deposits: a hope for earlier diagnosis?

-allows you to see AB in a living person

circadian rhythms in physiology

-almost all land animals have daily cycles of physiology, behavior -active period may be day (diurnal), night (nocturnal), dusk, etc -"entrained" (rest) by light via SCN

early attempts to control human aggression: psychosurgery

-amygdala removal surgery for violent offenders -frontal lobotomy used to treat psychosis, depression, neuroses (which also blunted emotional responses and thoughts, led to inappropriate behavior, and difficulty concentrating)

current theories of AD pathogenesis

-amyloid hypothesis (AB42 is part of trigger of what goes wrong) -tau hypothesis -myelin breakdown hypothesis -cholinergic hypothesis -infection hypothesis

histopathology of AD: amyloid plaques and neurofibrillary tangles

-amyloid plaques are made of AB (A beta) -defining features in Alzheimer's -extracellular -tangles are seen in many tauopathies (like CTE) -these are intracellular

autonomic effects of Epi-Pens

-anaphylaxis: hypotension, respiratory difficulty -epinephrine - sympathomimetic (artificial adrenaline) -constricts blood vessels (increases blood pressure) -increases heart rate (prevents cardiovascular collapse) -releases smooth muscle in lung -prevents release of histamines

summary of AD

-anatomical markers of AD: brain atrophy, plaques, tangles -causes of plaques: breakdown of APP -plaques may cause at least some symptoms of AD -plaques may predispose to tangles -hard to treat because late diagnosis/drugs don't enter brain/side effects/no definitive molecular target

the hypothalamus: activation correlates to sexual orientation

-androgen - hypothalamic activity in heterosexual women, homosexual men -anterior hypothalamus (sexual behavior) lesbians: -androgen doesn't activate hypothalamus -estrogen activation shares features with heterosexual males

some basic features of language (linguistics) - it's not just communication

-arbitrariness: no natural connection between representation and thing it denotes -productivity: meanings can be broadened, new signals for new ideas (primates) -displacement: communicate about things not present: spatially/temporally distant, real/unreal (bees) -cultural transmission (birds) -duality: minimal units (letters) combined in unlimited ways to form words/expressions (birds)

age-related myelin breakdown

-areas very heavily myelinated are some of the first to be affected in Alzheimer's

nondeclarative memory - habit learning, procedural memory

-associative: responses to sets of stimuli -classical (Pavlovian) conditioning - involuntary -operant (instrumental) conditioning - voluntary -non-associative: change in response to single stimulus -habituation, sensitization -HM could still learn new habits (hippocampal lesions disrupt formation of new DECLARATIVE memories) -striatum fires during habit performance -lesions of striatum disrupts formation of new procedural memories without affecting declarative memory

postganglionic pharmacology of the ANS

-autonomic motor neurons that trigger action (postganglionic cells - the autonomic motor neurons that actually trigger glands to secrete) -parasympathetic: ACh (very local) -sympathetic: NE (spreads)

infection/immune hypothesis

-bacteria (including Lyme-causing bacteria) and viruses found in brains of AD patients -parallels to neurosyphillis?

111 NFL brains: all but one had CTE

-biased sample - participants were suspected of suffering from CTE -still: higher rate among NFL players than general population -if 100% unexamined NFL brains were normal - then 110/1300 (9%)

patient SM: temporal lobe damage and emotional changes in humans

-bilateral amygdala damage -impaired recognition of fear in OTHERS -can still recognize happiness, sadness, disgust -fear and anger not recognized visually -still recognized in voices (may be secondary to not look at eyes) -impaired fear learning -impaired social judgements

removing temporal lobes in rhesus monkeys changes emotional behavior

-bilateral lesions reduces fear and aggression -appear "tame", approach and touch humans, let them stroke/pick them up -not afraid of natural enemies, like snakes -also have visual recognition deficits, oral tendencies, hypersexuality

amygdala (medial temporal lobe) = fear center

-bilateral lesions will reduce fear and aggression and impair recognition of emotional expression -fMRI activation when viewing fearful faces, but not happy or neutral faces -electrical stimulation produces fear (and other emotions)

testing animal models of amnesia: delayed non-match-to-sample task

-bilateral media temporal lobe lesions (hippocampus, amygdala, entorhinal cortex) impairs declarative memory and causes anterograde amnesia -working memory (seconds) intact

the addiction cycle

-binge (loss of control) -withdrawal -craving (expectation) -compulsion to seek and take drug -loss of control in limiting intake -negative emotion (anxiety, irritability) when no access (dependence)

epidemiology consistent with idea that maternal infection increases risk of schizophrenia

-birth cohort studies: increased risk with birth in winter or spring, influenza, rubella epidemics (2nd trimester) -issues: replication of results, defining exposure (recall, titers, diagnosis, treatment), defining schizophrenia

Dopaminergic projections are a critical element of the reward circuit

-blocking DA receptor reduces electrical self-stimulation -rats will also press levers to receive amphetamine injection (releases DA) -hungry rats press for food (reduced when blocked receptors) -natural rewards (food, water, sex) may reinforce behaviors that lead to these rewards via DA system

postsynaptic Ca2= influx via NMDARs linked to LTP at CA1 synapses

-blocking NMDARs prevents LTP, blocking postsynaptic Ca2+ rise blocks LTP -Ca2+ rise activates kinases (protein kinase C - PKC, CamKII) -phosphorylate AMPA receptors (increase current flow) -phosphorylates vesicle proteins (insertion of more AMPARs)

oxytocin, vasopressin, and promiscuity

-bonobos don't form monogamous sexual relationships, but chimps do -due to oxytocin and vasopressin receptor gene variation

studying modifications of synaptic strength which could store memory

-both increases/decreases in synaptic weight can store info

Why don't we move during our dreams?

-brain stem inhibits spinal motor neurons -REM sleep disorder - disruption of brainstem systems that mediate REM atonia

Which is true about APP?

-can be cleaved to form AB and P3

anger is a basic emotion

-can occur from frustration, hurt feelings, stress -can trigger aggression -in humans, anger can occur without aggression -in animals, unknown since aggression is the main way we measure anger

Motivation can be thought of as a driving force on behavior.

-capacity to work for a goal -probability and direction of a behavior gated by motivation -allows adaptation to internal, external change

amnesia

-causes: concussion, alcoholism, brain injury, encephalitis, tumor, stroke -dissociated amnesia: no other deficits -anterograde amnesia: no new memories (consolidation impaired) -retrograde amnesia: forget old memories (recall impaired) -transient global memories (changes in cerebral blood flow)

slide 10: cellular responses that promote peripheral nerve regeneration

-cells eat up the debris -in myelin wrapping, they inhibit outgrowth of neurons -if they don't get eaten up by macrophages, they prevent the growth cone from reinvading and reinneravating the new area -you can get regeneration/regrowth

neural circuit for aggression

-cerebral cortex -amygdala branches out to hypothalamus and PAG, ventral tegmental area -hypothalamus can also influence PAG, ventral tegmental area -PAG, ventral tegmental area leads to aggressive behavior

oxytocin

-childbirth, lactation -the love hormone -facilitates childbirth, maternal-infant bonding, milk release -empathy, generosity, trust, eye contact -favoritism and prejudice -low levels in some with autism predict social impairment -pair bonding, released by sex, orgasm

atypical antipsychotics

-clozapine, risperidone: don't act on D2Rs, more effective against negative symptoms -NMDAR agonists (severe side effects) -other targets largely unknown

Where were the rewarding electrodes stimulating? Mostly along the "reward pathway"

-clusters around reward circuit -VTA, nucleus accumbens -from and to prefrontal cortex -ALL DRUGS OF ABUSE HIJACK THE BRAIN'S NATURAL REWARD SYSTEM BY INCREASING DA LEVELS (spiral to addiction) -in addiction, DA connections strengthened so dorsal striatum is always on

stimulant drugs that target modulatory systems

-cocaine, amphetamine -both act on DA and NE synapses, sympathomimetic -increases heart rate, BP, pupil dilation -increased alertness, self-confidence, euphoria -cocaine blocks DA reuptake -amphetamines block NE and DA reuptake, stimulates DA release -prolong, intensifies effects of endogenous DA, NE -preventing DA/NE synthesis blocks effects of both -cocaine and amphetamine both lead to dependence (addiction) -enhanced transmission in mesocorticolimbic DA system (normally reinforces adaptive behaviors, diverted to reinforce drug-seeking behaviors)

innate vs motivated behaviors in body homeostasis

-cold, dehydrated hypothalamus, via hormones and sympathetic/parasympathetic innervation: -shivering, sends blood to core, reduces urine output, fat reserves tapped -motivated somatic motor actions: -move, drink water, eat, find shelter, make a fire, signal for help

addiction

-compulsive use of a substance or habit despite negative long term consequences -loss of self control -propensity to relapse -addiction co-opts an essential survival mechanism: motivation

reward prediction and reinforcement learning in reward circuits

-connections commonly active during or just before reward are strengthened -ex: food: sights, smells of food, drugs: finding dealer, legal drugs: tapping cigarette pack, beer being poured -to reduce risk of relapse, individuals need to avoid correlated events/signals/situations/people -reward prediction error may lead to extra intense craving

declarative memory

-conscious, declared, explicit -duration varies: working memory, short-term, long-term

maternal immune activation animal models of schizophrenia

-construct validity: based on suspected risk factor -face validity: recapitulates some symptoms of disorders -therapeutic predictive validity: responds to antipsychotics

Motivated somatic motor actions help ensure

-control of body temp in extreme conditions -food intake that meets energetic needs -water intake that maintains blood volume and chemistry -waste elimination -perpetuation of the species

the autonomic nervous system

-controlled by periventricular region of hypothalamus -widespread innervation of glands, smooth muscle, liber, pancreas, cardiac muscle, blood vessels, reproductive organs, immune response, bronchi of lungs -behaviors usually highly coordinated, autonomic (involuntary), relatively slow, excitatory or inhibitory

language processing in split-brain humans: if left brain doesn't know what right is seeing

-corpus callosum severed as last resort in some epilepsies -images presented to one hemisphere -right of fixation point (left hemisphere): can describe -left of fixation point (right hemisphere): cannot describe -comprehension intact if response is nonverbal

SCN keeps time using clock genes

-cortical EEG - rhythmic firing (due to thalamocortical circuits, ion channels) -SCN: rhythmic firing -due to rhythmic gene expression -clock genes - period, cryptochrome, clock (circadian locomotor output cycles kaput)... -similar clocks in other tissues - liver, king, lung, under SCN control

Don't suddenly stop taking prednisone: adrenal insufficiency

-cortisol inhibits release of ACTH -Prednisone is artificial cortisol, used to suppress inflammation -use should be tapered to avoid it -otherwise it shuts down release of CRH -feature of Addison's disease

leptin-deficient humans are usually obese

-crave food -slow metabolism -leptin replacement helps patients with leptin deficiency -doesn't affect most obesity -leptin often elevated in blood of obese, decreased leptin sensitivity in brain (perhaps not getting through BBB, not enough receptors for leptin, reduced responses to hypothalamus)

peripheral nerves but not central nerves can grow back together

-crocodile bit off arm -regeneration of peripheral nerves

narcolepsy

-daytime sleepiness, cataplexy, hallucinations, sleep paralysis, disrupted nocturnal sleep/sleepwalking -chronic, hard to diagnosis, rare and mimics other disorders (depression, infections, other sleep disorders) -affects males/females equally -loss of orexin-producing neurons in hypothalamus

critical periods for language are independent of mode of expression -there's also a critical period for song acquisition

-deaf infants babble with hands!

universality of language processing regardless of modality

-development: manual babbling in deaf infants happens at same age as verbal babbling in hearing infants -ASL speakers: left hemisphere damage has predicted effects, Broca's area: comprehension is good, production is impaired -hearing person who learned ASL: both languages impaired, recovered together after stroke

Why has it been so hard to find drugs to treat AD?

-diagnostic challenges -symptoms come years after pathology -only definitive diagnosis is post-mortem -BBB challenge - most drugs don't cross blood-brain barrier -side effect challenge: many proteins involved in pathology have other important functions (Y-secretase) -scientific challenge: no definitive proof that stopping plaques would stop cognitive symptoms -molecular challenge: AB peptides come in many forms

effects of brain stimulation on language

-differences suggest: -variability among brain areas that affect language in individuals -precise localization of specific aspects of language (naming, reading, grammar, jargon, facial movements) -dispersed coding of the same functions

brain activity associated with the basic emotions

-different activity hotspots, patterns for each emotion -some areas associated with multiple emotions

sleep is an active process: brain regions that regulate sleep-wake

-diffuse modulatory systems -brain stem NE, 5HT modulatory neurons fire when awake, ACh in wake/REM -control thalamic rhythms and subsequent sensory flow to cortex brain stem keeps us awake -lesions can cause state like non-REM sleep -stimulation can cause transition from non-REM sleep to alert

mechanistic models of schizophrenia: the dopamine hypothesis

-diffuse neuromodulator -evidence in support: -amphetamines cause dopamine release -amphetamine overdose mimics positive symptoms of schizophrenia

prolonged activation of acute response system (HPA axis: hypothalamic, pituitary, adrenal) may contribute to stress-related disorders in humans

-directs resources to active movement, away from maintenance, regeneration, reproduction -consequences can include slow growth in children, loss of libido, gastrointestinal problems, impaired disease resistance, slower rates of healing, depression, increased vulnerability to addiction

face blindness: prosopagnosia

-disorder of face perception -ability to recognize faces impaired -ability to recognize other objects usually intact causes: acute brain damage, congenital -2.5% of population, possibly 2-3 people in class can't recognize faces -can be caused by damage to temporal cortex

biological bases of affective disorders

-diverse symptoms: effects on mood, but also eating, sleeping, concentration -diffuse modulatory systems: HPA axis involvement?

PET (blood flow): areas in extrastriate, secondary auditory cortex specialized for words

-don't respond to non-word visual/auditory stimuli

reserpine treats positive symptoms of schizophrenia

-drug for hypertension -accidentally discovered to reduce hallucinations and delusions in schizophrenia -prevents serotonin, NE, dopamine from being packed into vesicles (inhibits VMAT - which pumps NT into vesicle) -generates PD-like motor symptoms

regulation of hippocampal glucocorticoid receptors by early sensory experience

-during critical period -lots of maternal care: more receptors -tactile stimulation also works -both activate ascending serotonin inputs to hippocampus -trigger lasting expression of glucocorticoid receptors (less CRH, less anxiety)

genetic factors in language impairments

-dyspraxia (inability to perform motor aspects of speech): FOXP2 -transcription factor affecting motor cortex, cerebellum, striatum -2 amino acids different in nonhuman primates -also expressed in bird areas involved in song learning -specific language impairment (SLI) -7% of 6 yr olds in US -language-learning delay, likely inherited -difficult time learning and using words -genes: FOXP2, CNTNAP2, KIAA0319 -dyslexia -learning disorder with difficulty reading, normal vision/intelligence -5-10% of people, men>women -strongly genetic, some overlap with SLI -aphasia -partial/complete loss of language ability after brain damage

after addiction cycle is broken, brain changes persist

-energy use reduced, particularly in frontal areas, even 100 days after last drug use

improving memory

-engaging in spatial memory may improve learning -mnemonics/method of loci/mental walk/"mind palace"

otoconia (ear stones)

-enhance tilt/linear acceleration sensitivity of otolith -vertigo: stones dislodged from gel of utricle, migrate into semicircular canals, interfere with fluid omvement -benign paroxysmal positional vertigo, with nystagmus -treatment: Canalith repositioning maneuvers

the dopamine hyperfunction hupothesis

-evidence in support: cocaine/amphetamines cause dopamine release, overdose mimics positive symptoms of schizophrenia -reserpine treats positive symptoms by preventing dopamine loading -chlorpromazine treats positive symptoms -this and other typical antipsychotics block D2 dopamine receptors -effective doses to block receptors, improve symptoms similar -PET scanning: higher DA correlates with psychosis

autism diagnoses increasing

-expanded definition of autism -more children being screened -financial incentives for schools to use autism label

face cells are common in some parts of inferotemporal cortex (IT)

-face-evoked brain activity -holistic face cell response -a face response in IT is not the sum of its parts

face inversion effect

-faces much harder to recognize if upside-down

creating false memories

-false memories can be created by directly activating hippocampal neurons during aversive stimuli ex: -cells active in box A, expresses "on switch" protein -box A cells turned on, shocked while in box B -animal now freezes in box A, creating a fear memory

PDAPP mouse model of AD

-familial Ad mutation in APP -overproduction of human AB42 (associated with Alzheimer's in humans) -causes some symptoms of AD - plaques, cognitive decline -limitations -no locus coeruleus (blue area in brain) neuron loss -no associative learning impairment -both young/old mice show deficits -low body temperatures

many diseases (including AD) have familial and sporadic forms

-familial: clear inheritance pattern (usually caused by single gene) -sporadic: more complex cause (environment, multiple genes) -familial AD is much less common -earlier onset (40-50) -genetic simplicity has contributed to understanding AD pathogenesis

proposed neural basis for fear learning

-fear learning: memories associated with fear (form quickly, long-lasting) -learning in the fear response -CS: tone -US: foot shock -UR: change in heart rate -pair tone (CS) with shock (US), tone (CS) by itself evokes fear response (UR) -reflected in recruitment of amygdala firing to tone -similar results in humans with visual stimulus - shock pairings

anxiety disorders: fear gone haywire

-fear/stress: adaptive response to threats -innate/learned -avoidance, vigilance, arousal -anxiety disorders: fear/stress response when not called for -HPA axis -autonomic (sympathetic) activation) - fight or flight -cortisol release from adrenal -corticotropin-releasing hormone (CRH) -CRH overexpression -> anxiety -CRH receptor deletion -> reduced anxiety

many models of AD pathogenesis, even more animal models of AD

-few species spontaneously develop AD-like symptoms -for experiments, 65+ years is too long -animal models each based on different hypotheses

leptin deficiency helps prevent starvation (at least if food is available)

-food craving stimulates feeding -slower metabolism conserves energy -inhibited reproduction (adaptive if food is scarce)

Apoe is a genetic risk factor for Alzheimer's

-found in plaques with AB -mutant allele e4 lowers median age of onset -20% of population has 1 e4 allele

melatonin

-from pineal, made from tryptophan -release inhibited by light -may help initiate/maintain sleep, regulate circadian rhythms -best for jet lag - bright light

norepinephrine system

-functions: attention, arousal, sleep-wake, learning, anxiety, pain, mood -cellular effects: increased excitability -disorder: chronic stress (affects HPA and NE) -nonadrenergic locus coeruleus -blue spot -fans out to innervate most of the brain -strongly activated by novel, nonpainful stimuli -general arousal/salience signal? (affects virtually all of the brain) -may speed processing by motor, sensory systems

serotonin system

-functions: pain, sleep-wake, mood, emotion -disease: depression -serotonin is synthesized from tryptophan

ACh system

-functions: sleep-wake, memory -disease: Alzheimer's Cholinergic basal forebrain and brainstem -ACh: also used by neuromuscular junction, autonomic ganglia, postganglionic parasympathetic synapses -modulatory forebrain complex -several nuclei in telencephalon -functions unknown: arousal, sleep-wake memory -among first neurons to die in Alzheimer's disease -pontomesencephalo-tegmental complex: acts on dorsal thalamus to regulate sensory relay nuclei

the uncanny valley: almost-faces are creepy

-gap between looking very cute and very creepy

hippocampus

-gateway to long-term declarative memory -other structures in medial temporal lobe also impilicated: entorhinal, perirhinal, parrahippocampal cortex -inputs: association areas of cortex -outputs: fornix -> hypothalamus

causes of schizophrenia: strong genetic component

-genetic linkages -sensory gating defect in schizophrenic maps near a7 nicotinic AChR -90% patients with schizophrenia smoke -a7nAChR agonists tested for therapeutic agent for schizohprenia

causes of autism

-genetics -environment: social isolation (orphanages), maternal infections -mercury (thimerosol) or other toxins/gut problems/diet/vaccines?

Long-term regulation of feeding NEEDS

-glucose deprivation as deadly as oxygen deprivation (food is less available than oxygen) -regulatory mechanisms store energy (anabolism) -glycogen (liver, skeletal muscle, finite capacity) -triglycerides (fat, virtually unlimited) -during fasting, broken down to release energy (catabolism) -feeding regulated based on energy reserves, rate of intake intake < expended - starvation intake > expended - obesity

Brain self-stimulation identifies sites potentially involved in reward in humans

-goes back to the rats! -reward goes haywire - addiction

otolith organs

-gravity, head tilt, linear acceleration (elevator, car start/stop)

place cells in hippocampus might result from summation of grid cells in entorhinal cortex

-grid cells fire at multiple locations arrayed on a grid -different cells have different grid sizes -could place cells be location of where a specific set of grid cells all fire?

vestibular system

-hair cells detect movement -direction selectivity depends on orientation of chamber -used for balance, equilibrium posture; coordinates eye/head movements (VOR) -disruption: motion sickness, disequilibrium, uncontrollable eye movements (nystagmus)

sleep-wake cycle free-runs in absence of time cues

-hard to remove ALL day/night cues (food, other people, heating) -internal clock >24 hours (24.5 to 25.5) -with time, can go 30-36 hours (20h awake, 12 sleep) -slip toward later bedtime without calibration -physiology stays on 24 hour cycle

semicircular canals

-head rotation, angular acceleration

Why do we eat?

-hedonic (feels good to eat, "like") - pleasure from taste, sight, smell -hunger: driving force behind food ("want, need") - craving -"liking" vs "wanting" mediated by different brain circuits

vaccines are a population-level strategy to reduce infections

-herd immunity required -not everyone can vaccinate (immunocompomised, very young, cancer/transplant patients) -low vaccination levels lead to outbreaks, even among vaccinated

newborn infants show preference for faces

-high degree of reaction for face, lower for scrambled, lower for blank

tetanic stimulation causes coincident pre and post synaptic activity

-high frequency stimulation -> temporal summation -stimulation of many synapses -> spatial summation (cooperativity) -result: if pre fires, post fires

specificity

-high frequency stimulation of one presynaptic input will only strengthen the stimulated input

psychiatric disorders have a genetic component

-high heritability for schizophrenia and bipolar -40% for depression and anxiety -high comorbidity between disorders -all psychiatric diseases are sporadic, not familial, which implies a complex genetic basis and possibly environmental influences

Hypothalamus is not required for motivated somatic motor actions.

-hypothalamus essential to innate homeostasis -rats with lesions of preoptic areas of hypothalamus, under cold stress: -no shivering, no changes in blood flow -but WILL learn to press a lever for hot air

both genetic and environmental factors can contribute to schizophrenia

-identical twin concordance rate is 50% -environment can be pre/postnatal -risk factors: poor maternal nutrition, stress, marijuana use, viral infections

neurodevelopmental disorder

-impairment of nervous system growth/development -emerges as individual grows (often first appear in infancy/early childhood) -if genetic and severe, usually caused by de novo mutations -classes of neurodevelopmental disorders include -intellectual disabilities (Down's syndrome) -autism spectrum disorders -communication deficits -attention deficit/hyperactivity disorders -learning disabilities (dyslexia) -motor disorders (Tourette's) -mood/affective disorders (schizophrenia) -multiple disorders frequently co-occur -may share similar underlying genetic causes

human pheromones: pathways for processing may be in hypothalamus

-in females: -estrogen activates olfactory -androgen activates hypothalamus -in males: -estrogen activates hypothalamus -androgen activates nothing

How are memories consolidated?

-in the case of LTP and LTD - phosphorylation of APMARs (problem: not permanent, phosphates removed, proteins turn over) -adding phosphates groups to a protein can change synaptic effectiveness and form a memory, but only as long as phosphates are attached (but phosphorylation isn't permanent, neither are the protein molecules) more persistent changes -persistently active protein kinases -new protein synthesis -changes in number, size (strength) of synapses

epilepsy: pathological synchronous activity

-increased excitation, reduced inhibition -activity patterns of muscle groups (ex: tonic, clonic, tonic-clonic, absence) -area: generalized (entire cortex, both hemispheres) or partial (circumscribed area - motor/sensory cortex, can cause deja vu, hallucinations, memory impairments)

temporal correlations between vaccination and autism

-individual: autism generally diagnosed around time of MMR -population: autism rates rose as vaccination rates rose -correlation, not causation

cortical differentiation to identify faces develops early

-infants activate same brain regions as adults when processing faces

in animals, again

-inhibitory synapses onto DA neurons lose ability to adaptively limit DA release after single drug exposure -also after cold-water stress -models relapse risk with re-exposure, stress

hypothalamus

-integrates information about the body's status -anticipates needs -provides coordinated hormonal and neural outputs

Donald Hebb's model of memory

-internal representation of object - all cortical cells it activates (cell assembly - simultaneously active neurons, cells are all interconnected) -if activation of the cell assembly persists long enough, consolidation occurs and these connections become more effective -distributed engram (less vulnerable to disruption) -involves neurons of sensation, perception -if only a fraction of the cells are later activated by a stimulus, the now-powerful reciprocal connections cause the whole assembly to become active and allow you to recall the entire internal representation of the external stimulus -Lashley, Hebb's mentor: info must pass through medial temporal lobe

drugs for depressive aspects of mood disorders

-iproniazid: inhibit MAO -imipramine: inhibits PMAT for NE -fluoxetine (Prozac) - inhibits PMAT for serotonin (SSRI)

serotonin deficiency may contribute to aggression

-isolated male mice: some become more aggressive -correlated with reduced serotonin turnover (synthesis, release, resynthesis) -females: no serotonin change, no aggression change -blocking serotonin synthesis/release increases aggression -involves reduced signaling via 5HT1A and 1B receptor subtypes -in children/adolescents, SSRIs sometimes associated with increased aggression, suicide risk (possibly by decreasing cortisol levels)

benzodiazepines (Valium) for anxiety disorders: "allosteric agonist" of GABAa receptors

-issues: overuse/addiction/increased dosage over time -alcohol also stimulates GABA action, reduces social anxiety; alcohol abuse common in anxiety disorders -valium and other sedating drugs like alcohol -> over-sedation, death -reduced benzodiazepine binding in patient with panic disorder: less GABARs?

candidates for fast-acting antidepressants

-ketamine: acutely: psychosis after: antidepressant -lithium: mood stabilizer (reduces depression and mania), monovalent cation, passes through Na+ channels, interferes with second messengers (PIP2, adenylyl cyclase) -deep brain stimulation (if ECT, drugs, therapy all fail)

early visual experience affects face processing

-kids born with cataracts in both eyes -blind for 2-6 months before cataract removal -tested after 9 years visual experience -can detect featural changes, but not configurational changes (ex: stretching the face)

vaccines aren't 100% effective

-known not to "take" in percentage of individuals -that's why MMR is repeated (booster) -population level: highly effective

critical periods for language

-language acquisition (begins at six months) -phoneme selectivity (ends at six months) - sounds can no longer be distinguished

hypothalamic lesions alter set point for feeding behavior

-lateral hypothalamus lesion: anorexia, starvation (no on signal) -ventromedial hypothalamus lesion: overeating and obesity (no off signal)

anatomy of the hypothalamus

-lateral, medial: connections to brainstem, telencephalon (motivation) -periventricular (innermost): most input from lateral and medial

Drugs of abuse "hijack" the brain's natural reward system

-learning mechanisms that reinforce natural rewards are hijacked -drugs cause pathological reinforcement of associated behaviors until they're exclusive/compulsive (rat lever press, brain stimulation button, drug/alcohol seeking) -memory trace created when DA levels high may underlie relapse

listening to speech: brain activity at 3 months resembles that seen in adults

-left hemisphere of temporal lobe -auditory areas/lateralization of language

cytokine IL-1

-levels track need for sleep -adding more promotes sleep -upregulated by infections

Dopamine neurons may encode errors in reward prediction

-light, then juice - DA neurons fire in response to juice -eventually, fire only to light and not juice -if no juice, firing drops -DA neuron code: as expected: no change better than expected: more firing worse than expected: less firing

babies!

-light/other timing cues fail to entrain their circadian rhythms in first few months -rhythms controlled by hypothalamus

the enteric division of the ANS

-lining of esophagus, stomach, intestines, pancreas, gallbladder -500 million neurons (same as spinal cord): sensory, interneurons, autonomic motor neurons -controls tension of walls, peristaltic movements, production of mucous and digestive enzymes, hormone levels in blood -receives sympathetic and parasympathetic input (stress inhibits digestion)

hypothalamic regulation of feeding behavior: one reason why diets don't work

-lipostatic hypothesis: brain monitors body fat and motivates action to defend it -or maybe fat tells brain cells when to eat? -drive to eat food after forced eating is reduced

engram

-location of a memory -long term memory = the engram

hypothalamus: roles in homeostasis

-maintains body temperature at 37C -cold: shiver (generates heat in muscles), goose bumps (fluff up your "fur" for better insulation), send blood to core -hot: sweat (evaporates), send blood to surface (heat radiates away) -blood volume, pressure, salinity, acidity, oxygen, glucose -regulates in response to changing environment

sham vs. predatory rage: induced by electrical stimulation

-medial hypothalamus - affective aggression, threat attack -lateral hypothalamus - predatory aggression, silent biting attack, requires posterior hypothalamus

HM taught us:

-medial temporal lobe -critical for consolidation (formation) of declarative memories, not required for retrieval -not required for all memories (working memory, formation/retention of procedural memory)

tau tangles

-medial temporal lobe for CTE looks brown -tau - brown -also seen in patients with Alzheimer's -just a correlate - not necessarily the cause

in inferior temporal cortex, cells gradually become more selectively response to particular face

-memory is distributed, same face evokes high activity in some cells, moderate/low in others -like population coding

types of memory

-memory: retention of learned information -declarative: memory of facts and events (explicit memory), more likely to be forgotten -episodic: autobiographical life experiences -semantic: facts -working memory: kept "in mind" -short term -> consolidation -> long term non-declarative: implicit memory, less likely to be forgotten procedural: skills, habits, behaviors -associative: association between two events ex: -classical conditioning - involuntary -instrumental learning (operant) - motivated -non-associative - change in response to a single stimulus (habituation, sensitization) -learning: acquisition of memories (new knowledge or skills) -amnesia: memory failure

challenges of molecular psychiatry

-mental illness diagnosed based on symptoms, cause often unknown -one diagnosis from many causes, drugs may not work in all patients in clinical trials -not all mental illness is genetic (even genetic disorders often linked to many genes, many forms (polygenic) or copy number variations (CNVs)) -one approach - study neurons from patients (derived from iPSCs)

Kluver-Bucy Syndrome

-mescaline produces hallucinations, temporal lobe seizures produce hallucinations -maybe temporal lobe is site of mescaline action -bilateral removal of temporal lobe in monkeys -could see, but can't recognize even previously familiar objects, or their use (visual agnosia) -would examine world with mouth instead of eyes (oral tendencies), developed desire to explore everything (hypermetamorphosis) -hypersexuality -emotionally dulled, facial expressions and vocalizations less expressive -reduced fear and aggression

monoamine hypothesis

-monoamines (include catecholamines - epinephrine, NE, DA) -hypothesis: accidentally discovery of drugs that affect mood -reserpine (BP drug) -prevents catecholamine, serotonin, from loading into vesicles -caused severe depression for some -TB drug (Iproniazid): inappropriately happy patients -monoamine oxidase (MAO) inhibitor (prevents destruction of catecholamines, serotonin) -both take long to take effect

high degree of heritability for AD according to twin studies (60-80)

-most AD caused combination of genes, some of which are "risk factors"

anxiety disorders

-most common psychiatric disorders -persistent worries that interfere with normal activities -includes panic disorders, phobias, OCD, GAD, PTSD -biological basis: genetics, experience (stress)

patterns of communication in the nervous system

-most other systems do point to point -secretory hypothalamus uses neurohormones -ANS has a body-wide network -diffuse modulatory systems have MASSIVE divergence

motion sickness - visual-vestibular mismatch

-motion felt but not seen (car, air sea) -motion seen but not felt (virtual reality, movies, space) -motion detected by both systems, but not matching (centrifugal gravity simulation, driving slow on a bad road)

vaccine for Alzheimer's

-mouse models: vaccination against AB can prevent formation of plaques -doesn't reverse existing plaques -can prevent neurite damage, don't always improve cognition -serious side effects

most APP mutations in familial AD are cleavage sites where secretases generate AB

-mutations probably affect ability of secretases to cleave -one of them reduces cleavage and protects against cognitive decline/Alzheimer's -others increase risk of Alzheimer's

mental illness and the brain

-neurology - diagnosis, treatment of nervous system disorders (MS, aphasia, nerve injury) -psychiatry - diagnosis, treatment of disorders of mind and behavior -traditionally, psychosocial approaches (psychoanalysis, behavior modification) -on the positive, it's destigmatizing (experience, not character, causes illness) -negative: "willpower can cure you!" -experience can modify brain structure and function

adenosine

-neuromodulator -levels track need for sleep -adding more promotes sleep -inhibits diffuse modulatory systems for ACh, NE, 5HT that promote wakefulness -caffeine, theophylline - adenosine receptor antagonists

cholinergic hypothesis

-neurons that make ACh are part of decline -dysfunction of ACh-containing neurons contributes to cognitive decline -basis for many treatment strategies/drug development approaches for AD to date

familial AD is inherited with mutant APP, suggesting that APP dysfunction causes symptoms of AD

-note -perhaps mutations in APP contribute to symptoms/diagnosis of AD -autosomal dominant

vestibulo-ocular reflex (VOR)

-on-board image stabilization for head tilt and rotation -vestibular input generates compensatory eye movements (eyes move in opposite direction to keep eyes fixed on a visual target) -keeps image stable on retina, despite movement -works in the dark

schizophrenia

-onset during adolescence/early adulthood -1% of population -symptoms: disruption of thought, perception, mood, movement -positive symptoms (add something) - hallucinations (voices), delusions (persecution), paranoia, disorganized speech, inability to tell reality from non-reality (psychosis) -negative symptoms (subtract something) - social withdrawal, flat affect and expression, lack of motivation, anhedonia, depression, memory impairment, deteriorating hygiene -divided mind - switch between normal and abnormal states

types of schizophrenia

-paranoid: auditory hallucinations (voices), delusions of grandeur, suspicion of being persecuted/spied on -disorganized: bizarre ideas, often about one's own body (bones melting), confused speech, childish behavior, emotional swings, neglect of hygiene and appearance -also: catatonic, residual, undifferentiated

roles of areas beyond medial temporal lobe in memory formation

-patient NA -left dorsomedial thalamus damage -severe anterograde amnesia, retrograde for 2 years prior to injury current hypothesis -required for formation of new memories (damage leads to anterograde amnesia) includes: hippocampus entorhinal, perirhinal cortex thalamus/mammillary body

H.M.

-patient whose experience led to insights about neural basis of learning/memory -experimental surgery for epilepsy, bilateral temporal lobe excision -removed hippocampus and surrounding regions -could never form "explicit memory" -long term memory impairments -anterograde amnesia -partial retrograde amnesia -explicit memory requires conscious thought (ex: remembering what you had for dinner last night, where you met someone)

hypothalamic motivation of feeding behavior

-periventricular hypothalamic neurons detect a drop in hormone released by fat cells -neurons in lateral hypothalamus stimulate feeding behavior

Cushing's disease: excess cortisol

-pituitary dysfunction -> elevated ACTH (and cortisol) -Cushings-like symptoms: common side effects of prednisone

place cells and grid cells - the brain's inner GPS

-place cells fire at a given location -grid cells are upstream, in entorhinal cortex -place cells firing replay during sleep -fire in sequence when running maze, same sequences observed during sleep

spatial memory: place cells and grid cells

-place cells fire at a given location -loss could impair memory of arms visited, platform location -London taxi drivers - larger posterior hippocampus -human place cells have activity in hippocampus when navigating in video game

associativity

-plasticity in one input can make nearby (spatially or temporally) inputs more susceptible to plasticity

definitive diagnosis of AD

-postmortem -neurofibrillary tangles and amyloid plaques (more concentrated in AD) -loss of synapses, axons/dendrites, neurons in selected brain regions atrophied cerebral hemispheres, dilated ventricles -note: hippocampus is basically gone

synapses in hippocampus are capable of "Hebbian" plasticity

-pre and post neuron fire action potentials at the same time, so synapse strengthens -different times, then it weakens

Hebbian plasticity can encode memory, but if left unchecked, will destroy memory storage (tends to saturate)

-pre/post coincidence - strengthened (LTP) -input now more likely to fire post neuron -more random coincidence with other inputs, more LTP -all inputs onto that neuron eventually strengthened -stimulus selectivity (memory) of plasticity lost -decorrelated pre/post firing - weakened (LTD) -input now less likely to fire post neuron -less coincidence, more LTP -some inputs completely silenced (no longer encode info) IN OTHER WORDS: -coincident weak inputs - summation -now both inputs sufficient to fire post, so it fires more often -higher chance another input will randomly fire at same time of post synaptic action potential -and now all inputs are strengthened

types of aggression

-predatory (for food) -few localizations -low sympathetic ANS activation -affective/sham (for show) -vocalizations -threatening/defensive posture -activation of sympathetic ANS -ex: cat hissing, arching back, hair on end, ears drawn back

face detection is rapid (~100ms)

-presented with series of different pictures -reaction time for faces is fastest

neuromodulators

-primarily bind to metabotropic receptors -modulate efficacy of glutamatergic or GABAergic synapses -released by populations of neurons that project broadly -regulate motor control, memory, mood, motivation, metabolism (broadly adjust neuronal excitability, synchrony) -DA, serotonin, NE, ACh

preganglionic pharmacology of the ANS

-primary NT of preganglionic autonomic neurons of sympathetic and parasympathetic divisions: ACh -acts on nAChRs (muscle) - fast excitatory EPSP -mAChRs - slow EPSPs and IPSPs -also releases: NPY, VIP: GPCRs, slow, modulatory

how to test drugs that block plaque formation in mice for safety/efficacy

-problem: mice don't get plaques, only live two years -what happens if mice are engineered to express familial AD version of APP

treatments of anxiety disorder

-psychotherapy -anxiolytic medication (benzodiazepines, SSRIs)

animal models of addiction

-rats press a lever to receive cocaine -press more frequently, even when shocked -models compulsive and self-harming aspects of addiction -implanted electrodes stimulated when lever pressed -electrodes in some region: pressed so much they didn't eat or dink, stopped only when collapsed

modifying existing memories: reconsolidation

-reactivating memories may make them vulnerable to modification/erasure -of concern in witness testimony, treating PTSD

double-dissociation of face vs. object recognition: patient C.K.

-recognizes faces, but not objets -double-dissociation suggests dedicated machinery for face processing -face made up of fruit -can see face, cannot identify fruit

vasopressin

-regulates blood volume and salt concentration -antidiuretic hormone -acts directly on kidneys -low water: low blood volume, high salt -triggers vasopressin release -kidneys reduce urine production -low blood volume/pressure: -kidneys trigger generation of angiotensin II (kidneys secrete renin, then angiotensinogen , angiotensin I, II) -acts on subfornical organ -> lateral hypothalamus -> thirst, increased vasopressin production

leptin

-released by fat cells -acts on neurons of hypothalamus that decrease appetite, increase energy expenditure -treating ob/ob mice with leptin reverses eating disorder and obesity -increase in leptin inhibits feeding, increases metabolism -decrease in leptin increases feeding, decreases metabolism

neurohormones

-released into blood by neurons -a neurosecretory cell can release a neurohormone into circulation via blood, or close to target cells without intervention of bloodstream

autism

-repetitive behavior -impaired social interactions/communication -spectrum disorder - affects each individual differently -4x more common in boys than girls -usually diagnosed in first few years of life -most common of PDDs -seen in every demographic -deficits in communication, reciprocal social interactions -reduced sharing of interests/emotions -restricted/repetitive activities, adherence to routine -difficulty adapting to new environments -intelligence/ability spectrum 70% intellectual disability, 30% normal/high intelligence a few have exceptional abilities in math, music, memory, art

support for Cannon-Bard - emotion without perception

-responses to emotions without being aware of it -perception: expressionless face, ANS: no effect -perception: angry face with unpleasant sound, ANS: increased skin conductance -perception: expressionless face right after angry face, ANS: increased skin conductance (and amygdala activity) -demonstrates an autonomic response

sleep training

-rewards timed with firing of given place cell cause awake animal to go to encoded place -animal goes to paired place cell that was paired with reward during sleep

Addiction: reward often pursued despite harm to self or others

-risk of addiction not eliminated by understanding risks, family support, education, etc. -genetic modifiers of risk, but anyone can become addicted

Why is distributed memory storage useful?

-robust: loss of individual cells/synapses unlikely to destroy memory -with cell death: graceful deterioration (memories blended, conflated) -implication: changes in synaptic weights can shift selectivity (store information)

psychiatric disorders: summary of pharmacology of treatment options

-schizophrenia (D2R antagonists) -mood disorders (SSRIs) -anxiety disorders (GABAa agonists) -addiction: very few treatments

Parvocellular secretory cells project (via bloodstream) to anterior pituitary.

-secrete corticotropin-releasing hormone (CRH) -triggers release of corticotropin, or adrenocorticotropic hormone (ACTH) -ACTH triggers cortisol release from adrenal cortex

motivation: sensory predictions of needs, learned behaviors that help meet them

-sensory input: diverse neuronal measurements of stomach stretch, blood glucose -innate brain prediction: energetic needs may soon not be met -motivation provided: I'm hungry (ghrelin increases hunger, gut motility) -learned behavior: run for cookies at break -reward: food

Serotonin is also involved in control of feeding behavior.

-serotonin (anti-depressant effect) synthesized from eating tryptophan -eating leads to mood elevation -drugs that increase serotonin, like SSRIs, promote weight loss -appetite suppressant -we don't need more tryptophan to make serotonin, we have enough

vaccines should make you feel crummy

-should stimulate robust systemic immune response -includes cytokines -should cause fever, aches, lethargy, local swelling

Glutamate and GABA have immediate, local effects by binding to ionotropic receptors.

-slower, more lasting effects via metabotropic receptors IMPORTANT -class of NT called "neuromodulators" primarily bind to metabotropic receptors.

common features of diffuse modulatory systems

-small "core" (few thousand neurons), most in brainstem -massive divergence: one axon may contact >100,000 neurons -release NT into extracellular fluid, not synaptic cleft -volume transmission -can tune an entire brain region

short-term control of feeding behavior

-social/cultural factors: you eat when you're nervous

language

-sounds, gestures for communication -also written language, but requires extensive formal training -universal feature of humans, >5000 languages/dialects -perception: auditory, visual (McGurk effect) -production: motor -involves >100 muscles of lungs, laryns, mouth -nearly all cannot be seen in action -nonhuman primates: higher larynx makes speech impossible (so what?)

3 properties of LTP at CA3 -> CA1 synpases

-specificity -cooperativity -associativity

How does fat talk to the brain? Blood!

-spontaneous mouse mutation -> obesity -encodes protein that signals normal fat reserves (leptin)

cortisol: chemical control of brain and behavior

-steroid hormone that travels throughout body -receptors widely distributed in the brain -suppresses immune system, decreases serotonin, decreases sensitivity to pain, increases BP, heightened memory and attention, increases blood sugar -basically, your fight or flight response

problems with Wernicke-Geschwind model

-still arguing about where things are -visual info doesn't have to pass through angular gyrus -aphasia severity affected by cortex beyond Wernicke's and Broca's -most aphasias involve both comprehension and production -what about subcortical structures, or recovery after damage?

The almost-reward: the most addicting reward?

-stimulate brain and giving them the sensation of ALMOST reward

evidence for role of human medial temporal lobe in episodic memory

-stimulation appears to trigger recollections -electrical stimulation in patients -temporal lobe epilepsy: feelings of familiarity, infamiliarity, recollections/flashbacks -recordings show neurons with preferential responses to categories of objects, or specific people/places -lesions disrupt memory (H.M.)

face patches - fusiform face area

-stimulation of FFA distorts face perception -face "metamorphosed"

Like cocaine, a dopamine neuron can reinforce an arbitrary action (operant conditioning)

-stimulation of rat medial forebrain bundle (connects VTA to nucleus accumbens) -cause pathological reinforcement of behavior just before you got the drug

human fMRI imaging of native/non-native language use

-storage of language is different if you learn it late -no overlap in Broca's, but overlap in comprehension -stroke: in bilingual people, effects on language depends on when learned, fluency, how recently used

genetics of autism

-strongly genetic -sibling with autism, 25x risk -genome wide association studies (GWAS) - many gene variants associated with risk -regulate synapse development/function, transcription, chromatin -specific syndromes with overlapping symptoms (syndromic autism) -relatively rare -single gene, 100% penetrant -allow generation of animal models

the cruel homeostasis of addiction: tolerance

-substances/behaviors that stimulate DA release in NAc are strongly enforced -chronic overstimulation of pathway: responses homeostatically downregulated -increases tolerance - more drug to feel effect -withdrawal - endogenous signals no longer sufficient -perhaps due to reduced dopamine receptor availability (lower in addiction)

Deep brain stimulation in Parkinson's: addiction to morphine-like self-stimulation

-substantia nigra deep brain stimulation implant for Parkinson's -kept going back for morphine-like effect, asking them to turn it up

AB42 prevents high frequency stimulation from generating hippocampal LTP

-suggests potential link between AB42 and learning/memory -synapse does not strengthen -might represent change in ability to store info at a single synapse

facial expression vs identity are processed in different areas

-superior temporal sulcus (STS) - expression-selective -inferior temporal cortex (IT) - identity selective

The Papez circuit: one proposed "emotion system"

-support: damage to cortex can alter emotional expression (e.g.: Phineas Gage) -cortex and hypothalamus directly influence each other - links expression and experience -bidirectional between hypothalamus and cortex: compatible with both JL/CB current theory: there are multiple, non-discrete emotion systems -we don't know if emotion is represented in activity in a specialized brain area, network of areas, or more diffuse network -cortex is critically involved in emotion

tau hypothesis

-tau is a cytoskeleton -assemble into pipes that form cytoskeleton of neuron -tau abnormalities are a trigger -collapse of neuronal transport system -some dementias only have tangles, no AB plaques (so plaques aren't required for Alzheimer's) -expressing familial AD APP increases tangles, but only in mice expressing mutant tau

thalamocortical rhythms generated by intrinsic properties as well as connections in thalamus

-thalamic rhythms create sleep spindles -we don't know what cortical rhythms do theories -disconnect cortex from sensory input -fast rhythms in awake cortex: coordinate activity across sensory, motor regions -accidental by-product of circuit structure (feedback)

the secretory hypothalamus

-thalamus: routes sensory and motor information to neocortex, lesions cause localized deficits -hypothalamus: integrates somatic and visceral responses, lesions cause widespread effects and death

What do hippocampal LTD and LTP (synaptic plasticity) have to do with memory?

-theory: synaptic plasticity can encode declarative memories -correlative support: LTP in CA1 induced by learning -NMDARs required for LTP/LTD, and for learning -blocking them blocks LTP/LTD/learning -overexpressing NMDARs may improve memory

treatments for schizophrenia

-therapy -exercise, healthy diet, avoiding alcohol, sleep -cognitive techniques (identifying triggers, controlling sensory inputs, confronting/ignoring hallucinations) -typical antipsychotics -target D2 receptor (reduces positive symptoms) -side effects: drowsiness, weight gain, jitters, movement problems (PD-like) -long term - tardive dyskinesia: uncontrollable movements

another way to measure neuronal population rhythms: magnetoencephalography (MEG)

-tiny magnetic fields induced by neuronal current flow -localizing: fMRI>MEG>EEG -speed: MEG or EEG > fMRI or PET -measure activity: EEG, MEG -measure metabolism: fMRI, PET

aggression: why

-to kill for food, defend offspring, win mate, scare off rival (social hierarchy) -influenced by levels of male sex hormones (androgens) -in animals: seasonal correlation, adding testosterone increases aggression, castration reduces it

animal language: mimicry

-trained (operant conditioning) -Hoover the Harbor seal - thick Maine accent -dolphins (Hello Margaret) -African gray parrots

Animal language: Koko and ASL/GSL

-trained: Koko the Gorilla -taught Koko ASL -knows >1100 signs; understands meanings -invents compound/phonetic signs (brow "S") -understands spoken English -also: Washoe the chimp, Kanzai the bonobo -spoken language not required for intelligence

working memory

-transient, small capacity, usually requires rehearsal -replay circuit kept alive: no lasting storage -capability of many regions of neocortex, including prefrontal cortex -PFC needed for delayed-response tasks, Wisconsin card-sorting task, tracing mazes (all use working memory)

Natural rewards (food, etc)

-unexpected reward increases DA (learn where that came from) -predicted rewards don't increase DA (I already know how to get that) -learning optimized -drive to seek predictable rewards remains under homeostatic regulation

grid cells: brain's inner GPS

-upstream of hippocampus, in entorhinal cortex -respond when animal is at multiple locations that form a hexagonal grid -different grid cells have different grid spacings

a dimensional representation of basic emotions

-valence and arousal and fundamental properties of emotion -two axes: arousal (how active or attentive you are) and valence (is it positive or negative) example: high arousal, positive valence - smiling baby low arousal, no valence - chair

antidepressants increase glucocorticoid receptors in hippocampus

-via regulation of gene expression (slow) -we need rapidly-acting antidepressants

EEG scalp neurons measure synchrony across neurons

-voltages from single neurons are too small to measure in EEG -synchrony allows rhythms to be measured

pareidolia

-we see faces everywhere (but only if they're right-side up)

hollow-face illusion

-we tend to see face representations as convex

BCM model: learning rules to strengthen/weaken synapses

-weak presynaptic firing (no postsynaptic action potential) - out of synch, lose your link -strong presynaptic firing (triggers post synaptic action potential) - fire together, wire together -homosynaptic: happens to synapse being stimulated -also seen in IT cortex

spike-timing dependent plasticity (STDP), fire together, wire together

-when postsynaptic spikes follow EPSPs, synapse is stronger -when postsynaptic spikes precede EPSPs, synapse is weaker

leptin levels influence hypothalamus-regulated feeding behaviors

-with food: high leptin -after food: low leptin

memory consolidation

-working memory: small capacity, lost by distraction, requires rehearsal (phone number) -short term memory: large capacity, survives distraction, no rehearsal (what you had for breakfast) -short term memory - sensory info physically modifies brain in transient way -synaptic transmission transiently altered -some memories selected for long-term storage by consolidation through different mechanisms -long term memory - relatively stable over time, new gene expression and protein synthesis -> lasting changes in synapses

Why do we dream? Who knows!

But it seems important -depriving REM sleep -> REM rebound, impairs learning Theories -Freud: fulfill suppressed wishes (aggressive, sexual, overcome anxiety) -overcome to understand subconscious! -to remember (REM sleep improves some memory performance) -to forget (remove useless connections) -to keep brain working (continual activation theory) -to rehearse (practice fight or flight) -to heal (lower stress hormones in rem; reviewing trauma helps process) -to solve problems (unconstrained by logic) -activation-synthesis hypothesis: dreams are an accident, random discharges of pons trigger associations from cerebral cortex

long-term effects of SSRI's and other drugs that target monoamines

HPA axis -genetic/environmental factors converge -both are risk factors for mood disorders -HPA over-activity seen in depression (elevated cortisol, CRH) -injecting CRH causes symptoms of depression (sufficient) -insomnia, decreased appetite, increased anxiety (comorbidity) -hippocampal glucocorticoid receptor activation -> negative feedback to HPA axis (hippocampus suppresses CRH release) (glucocorticoid receptors respond to cortisol, inhibits CRH release) -but not in depression, you have fewer receptors

hypothesized neural substrate of learning and memory

Hypothesis I: memory is stored in different strengths of synaptic connections in neural circuits. Hypothesis II: learning modifies synaptic strength.

emotional expression and experience - which comes first?

James-Lange: stimulus -> autonomic arousal and behavioral responses -> conscious emotion of fear (emotion is experienced in response to physiological changes) Cannon-Bard: stimulus -> subcortical activity in thalamus -> autonomic arousal and conscious emotion of fear (emotional experience can occur independently of emotional expression)

Neurons of the posterior pituitary release neurohormones into the bloodstream.

Just a note.

Motivation uses past experience to help predict the likelihood of an occurrence.

Pavlovian conditioning -neural stimulus (bell) paired with potent stimulus (food) -NS comes to elicit same response (salivation) elicited by potent stimulus goal-directed instrumental (operant) conditioning -learning through consequences of behavior -conscious changes in behavior to increase reward (rats press lever to receive cocaine)

SSRIs

Prozac, Zoloft, Paxil -used for depression, also effective in treating anxiety -serotonin transporter mutation found in family with OCD -effects develop slowly -not due to rise in extracellular serotonin, but an unknow adaptation to higher serotonin -perhaps, increased glucocorticoid receptors in hippocampus?

PET scans: wake, REM, non-REM, all associated with different brain activation

REM, wake: -visual cortex equally active in both -limbic, extrastriate cortex more active in REM -frontal lobes less active in REM REM, non: -visual cortex less active in REM (no vision) -extrastriate more active in REM (internal processing areas: internal vision - dreaming?) -limbic more active in REM (emotional component) -frontal low (uninterpreted imagery)

two face processing streams: one for identity, one for changeable aspects of the face

STS linked to amygdala, insula, limbic system (all of which deal with emotion)

Animals appear to express some of the same emotions as humans.

Theory: emotions free animals from stereotypical, brainstem-driven responses

Magnocellular secretory cells project to the posterior pituitary.

These cells release two neurohormones: -oxytocin -vasopressin/ADH

Why do we sleep?

Who knows? But it must be important! -vulnerable to predation -even animals that can't stop moving do sleep -dolphins: half hemispheres -muddy river dolphins: microsleeps (4-6 sec) -worker ants: 250x 1 minute power naps -theories: -restoration (recover - but not tissue repair) -adaptation (hide from predators, conserve energy) -sleep deprivation can lead to cognitive impairment

What if brain areas that help you predict and meet essential physiological needs are hijacked? What if they motivate you to seek things you don't need or are harmful?

addiction

mood disorders and creativity

affective disorders 10-30x more common in highly creative people -hypomania: increased creativity, productivity self-confidence

what controls (or mis-controls) the HPA axis?

amygdala and hippocampus amygdala activation triggers stress response hippocampal activation suppresses CRH release -in response to cortisol from adrenal (negative feedback) -chronic stress can impair suppression

immediate reactions to eating (three phases)

cephalic -sight and smell: anticipation -ANS activated (parasympathetic, enteric) gastric -chewing, swallowing, filling stomach substrate -nutrient absorption via intestine -satiety signals (FULL): get food in and increases -orexigenic signals (EAT): fall -NOTE: -drive to eat increased by orexigenic signals in response to fasting, inhibited by satiety signals that occur once we begin to digest

plasticity

change in action potential firing in response to a given stimulus

Which neuromodulatory system is most implicated in schizophrenia?

dopamine

How early in development are signs of autism evident?

early correlates -brain structure differences in premature babies -early postnatal macrocephaly -behavioral differences as early as 2 months, impaired biological motion detection at age 2

Duchenne: emotional expressions triggered by electrical stimulation

eh

Emotional expression in robots, felt in the body (hot headed, cold feet)

eh

biological benefits of sleep

energy conservation -respiration, body temp, BP, heart rate, muscle tension niche adaptation -avoid predators (sleep when most vulnerable) body restoration -replenish proteins and other metabolic requirements -GH released during SWS -sleep essential for immune function memory consolidation -reduce memory interference, decay -actively contribute to learning

two aspects of emotion: expression and experience

expression -behavioral: blushing, laughing, crying, running -physiological: heart rate, skin conductance, neural activity experience -subjective feelings of humans -linguistic, conscious

normal EEG

generally -high frequency, low amplitude (low synchrony) = alertness, waking, dreaming (gamma, beta) -low frequency, high amplitude (high synchrony) = nondreaming, drugged coma

regulators of appetite and satiety

ghrelin -hunger is not just lack of satiety -concentrated in stomach, released when empty -stimulates NPY/AgRP-containing neurons of arcuate (also activated by drop in leptin) - stimulates appetite and food consumption gastric distension -mechanosensory axons sense stretch (vagus nerve) -activate neurons in nucleus of solitary tract -also site of gustatory nucleus, ANS control cholecystokinin -in intestine, enteric nervous system -satiety signal that acts on vagus nerve insulin -glucose transport into non-neuronal cells requires insulin -anabolic: promotes glucose storage in liver/fat

Faces are special!

guide social interactions -identify and bond with caregivers -key site of emotional expression/mood -dominance hierarchy cues -recognize potential mates' gender, age, health/fitness, attention/interest -when face expectations aren't met, we find it difficult to process

animal language

innate -honey bees: dance conveys orientation, distance, and quality of food source -chimps: tens of vocalizations, dozens of gestures (little evidence of phonological rules) -dolphins: conversational exchanges, up to five "words" at a time

LTP persists as long as we can record

just a note

The pituitary gland is the gateway to brain-body connection.

just a note!

EEG rhythms similar across species

just a thought

synaptic homeostasis: a summary

low activity -scaling-up synaptic strength -shift in modification threshold to favor LTP high activity -scaling-down of synaptic strength -shift in modification threshold to favor LTD

amygdala activity associated with enhanced emotional memory

more activity in amygdala -with pleasant/aversive than neutral images -when recalling pleasant/aversive images they had seen -pleasant/aversive images - better recall

degenerative disorders of the adult nervous system

neurodegenerative disorders -progressive disorders, can affect balance, movement, talking, breathing, heart function (like affective disorders, can affect "who we are": mood, cognition, personality -causes: genetic, alcoholism, tumor, stroke, toxins, chemicals, viruses (for many, cause is unknown) -treatments: for symptoms (most have no cures) younger adults, e.g.: -nerve injury -chronic traumatic encephalopathy (CTE) -amyotrophic lateral sclerosis (ALS) -multiple sclerosis (MS) older adults, e.g.: -Alzheimer's -Parkinson's -Huntington's

APP is cleaved by secretases, and that makes AB (which is basically pieces of APP)

note

Memory impairment comes after the formation of tangles and plaques.

note

age distribution of American population: disorders of aging will rise

note

apes and monkeys also imitate facial expressions

note

cooperativity and Hebbian LTP can cause selective strengthening of associated synapses

note

dogs and sheep have advanced face-recognition abilities

note

face orientation profoundly affects feature recognition - Thatcher effect

note

face recognition works despite enormous variation in portrayals

note

human fetuses produce facial expression

note

loss of cortical gray matter in adolescence patients with schizophrenia, major neuroanatomical differences between patients with schizophrenia and their identical twins

note

neurons encode information in the frequency of their firing, and learning is the persistent change in firing to a given input

note

not all animals that sleep seem to dream

note

serotonin, NE, DA: neuromodulatory systems involved in diverse psychiatric disorders

note

some face cells are sensitive to expressions

note

EEG rhythm frequencies nearly invariant across brain sizes

notes

simple rhythm generators: one- and two-neuron oscillators

one-neuron oscillator - voltage gated channels two-neuron oscillator - alternate firing from constant drive (there's a constantly active excitatory input)

during LTP, synapses get physically bigger and may increase in number

ote

How is learning a second language different from learning a first?

production of a non-native language is encoded separately from a native one

treating Alzheimer's

rational drug discovery -interfere with AB production by inhibiting B-secretase (which cuts up AB) -chemical compounds or antibody that inhibits B-secretase -wild type animals as models -test in human clincal trials

declarative memory functions of hippocampal system

roles in: -binding sensory info for memory consolidation -spatial memory of where objects are -storage of memory -duration - under debate -testing memory in rodents: radial arm maze, Morris water maze -hippocampal lesions: revisit same arms (working memory deficit) -fail to remember platform location in water maze

Neural outputs of the nervous system

somatic motor system -controls skeletal muscle fibers -monosynaptic (lower motor neurons in spinal cord or brain stem) autonomic nervous system -every other innervated tissue, organ -disynaptic (not counting input from hypothalamus) -preganglionic neurons in spinal cord and brainstem, which drive the -postganglionic neurons (lower motor neurons) lie outside the CNS in cell clusters called autonomic ganglia -autonomic ganglion can be sympathetic or parasympathetic

periventricular hypothalamus (what the cells in them do)

suprachiasmatic nucleus (SCN) -receives direct retinal input -synchronizes circadian rhythms with light/dark cycle controls autonomic nervous system -regulates sympathetic, parasympathetic innervation of organs neurosecretory organs project to the pituitary gland

sympathetic versus parasympathetic nervous systems

sympathetic -preganglionic neurons from middle third of spinal cord -crisis (real or perceived) -four F's: flight, fight, fright, and...sex parasympathetic -preganglionic neurons from brainstem, sacral spine -digestion, growth, immunity, energy storage -rest and digest -two systems are physiologically opposed, reciprocally activated -many organs innervated by both: -heart: sympathetic increase, parasympathetic decrease -gut: parasympathetic increase, sympathetic decrease -penis: erection is parasympathetic, ejaculation is sympathetic (stress increases sympathetic tone, leads to impotence and premature ejaculation) Some are innervated by one: -blood vessels, sweat: sympathetic increase -tear glands: parasympathetic increase

autonomic effects of drugs

sympathomimetic drugs: -stimulate NE (adrenaline) or inhibit mAChRs -atropine: mAChR antagonist, increases sympathetic activation (increases heart rate, dilates pupils) parasympathomimetic drugs -inhibit NE or stimulate mAChRs -propranolol - NE receptor antagonist, used for stage fright

consolidation: memories may migrate from hippocampus to cortex over time

theory: hippocampus forms and stores new memories -old memories transferred to cortex -HM: lost hippocampus, anterograde amnesia