Bio of the brain, block 3

Describe the location of the suprachiasmatic nucleus?

-In humans (and other mammals), the circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus (dense, paired structure at bottom of brain in the anterior hypothalamus)

What is the difference between semantic and episodic declarative memory.

-"Facts"- Semantic: Facts, knowledge about the world we can express in words -"Events"- Episodic: An episode, scene of events; often autobiographical -4 Steps in declarative memory: 1.) Encoding: New information is acquired and linked to established information; attention and motivation is important for encoding memory 2.) Storage: Mechanisms through which memory is retained over time- short-term is limited; long term is vast 3.) Consolidation: Mechanisms through which temporarily-stored info is made more stable 4.) Retrieval: Process by which stored information is recalled; retrieval may depend on how the information was encoded

Describe the characteristics of Kleine-Levin Syndrome

-"Sleeping-beauty syndrome"- very rare sleep disorder -Characterized by recurrent, severe hypersomnia (15-20 hours of sleep/day) -Episodes last days, weeks, months, often re-occur -Cognitive and behavioral disturbances during wakefulness: ->Confusion, disorientation ->Hallucinations ->Binge-eating ->Hypersexuality

During what time of day would you be most likely to see high locomotor activity in a running wheel analysis of mouse circadian behavior?

-Nocturnal rodents (rats, hamsters, mice, etc.) are active at night, inactive in the day ->When active, many rodents love running on running-wheels ->Running-wheel activity is a particularly reliable and convenient measure of the output of the master circadian clock

Describe the anatomical boundaries of the hypothalamus. Anterior hypothalamus (below what, lateral/medial preoptic, position of suprachiasmatic nucleus, optic chiasm, third ventricle), Tuberal hypothalamus (the two sections, state of third ventricle + optic chiasm in each, unique nuclei)

-Anterior, Tuberal (main), and Lateral-posterior regions of defined hypothalamic nuclei clusters Anterior hypothalamus: -Located below the anterior commissure; region is referred to as the Preoptic -Lateral preoptic nucleus sitting on the sides, medial preoptic nucleus towards midline -Suprachiasmatic nucleus sits on the bottom of the anterior hypothalamus and above the optic chiasm (bottom part): -Optic chiasm: Thick bundle of axons from the retinal ganglion cells, a small subset of which go to the suprachiasmatic nucleus -Third ventricle splits in two to form "midline" Tuberal Hypothalamus (anterior portion): -Third ventricle maintained as midline -Paraventricular, anterior, lateral, and supraoptic nucleus -Optic chiasm retained Tuberal Hypothalamus (posterior portion): -Third ventricle retained -Dorsomedial, ventromedial, and lateral nuclei -Optic chiasm split into optic tracts Lateral-posterior hypothalamus ("back end"): -Lateral nucleus -Prominent: Mammillary Body- Paired structure; "unhypothalamic" function akin to a limbic structure, despite being contiguous with the hypothalamus Involved in memory

What is the difference between circadian, ultradian and infradian rhythms?

-Circadian rhythms: Endogenously-generated rhythms with a period close to 24 hours. May or may not be synchronized with the day/night cycle. -Diurnal rhythms: A circadian rhythm that is synchronized with the day/night cycle -Ultradian rhythms: Biological rhythms with a period much shorter (i.e, frequency much higher) than 24 hours →Blood circulation, blinking, pulse, hormonal release, heart rate, thermoregulation, urination, bowel activity, feeding, etc. -Infradian rhythms: Biological rhythms with a cycle of much longer than 24 hours →Menstrual cycle, seasonal changes in physiology and behavior, hibernation, migration, etc.

Describe 3 key features of the flip-flop switch model of sleep regulation.

-Components of the ascending arousal system (hypothalamus and brainstem) and the VLPO (hypothalamus) are interconnected and mutually inhibitory -Mutual inhibition causes abrupt, stable state changes and resists transitional states (analogous to an electronic flip-flop switch) ->"Wake-on" populations cause the brain to wake while inhibiting "wake-off" populations, and vice-versa (activity on one side invokes "disinhibition" → turning off neurons that would turn it off) ->"See-saw"- weight shifts and falls into one state or the other; no "transitional zone" ->Orexin neurons stabilize the wake state

What information does the hypothalamus integrate in order to homeostatically defend physiological set points?

-Contextual info (cerebral cortex, amygdala, hippocampal formation) and Sensory (visceral, somatic sensory pathways; chemosensory and humoral signals) info input to the hypothalamus, which compares those inputs to biological set points ->It then induces visceral motor, somatic motor, neuroendocrine, and behavioral responses

Describe four ways in which LTP is well-suited to being a mechanism for information storage in the brain. (Cooperativity, associativity, synapse specificity, persistence)

-Cooperativity: Several weak (subthreshold) inputs, which wouldn't individually elicit an LTP, are activated simultaneously, which produces a suprathreshold EPSP → postsynaptic AP ->LTP in all activated pathways ->Even weak stimuli can be retained when arriving closely-spaced in time -Associativity: Stimulation of strong and weak inputs simultaneously ->Produces a suprathreshold EPSP → postsynaptic AP ->LTP in all activated pathways →In this way, a weak input becomes significant when paired with a powerful one -Synapse specificity: An unstimulated pathway does NOT undergo LTP in spite of strong stimulation of neighboring synapses ->Information is stored only at activated synapses following strong stimuli -Persistence: In vivo recordings show that LTP can be maintained from an hour to >1 year

What do the hamster transplantation experiments tell us about the function of the SCN?

-Discovery of a spontaneous monogenic mutation in golden hamsters giving rise to free-running rhythms with short circadian periods (tau) ->Wild type hamsters have a period of 24 hours ->Homozygous Tau mutants have a period of 20 hours and an abnormal entrainment to light →Suggests genetic basis for period -WT hamster had its SCN replaced with that of a Tau mutant, and vice versa (reciprocal SCN transplantations) ->The hosts began to display the periods associated with their SCN donor → complete phenotypic switch →Circadian period length is determined by the SCN and has a genetic basis

Which sleep stage is accompanied by atonia? Describe the polysynaptic circuit that produces atonia during REM sleep

-During REM sleep, we experience almost complete muscle paralysis: REM atonia Polysynaptic circuit that produces atonia during REM sleep: -Specific region of Pons: Sublaterodorsal nucleus (SLD); "REM-ON" excitatory neurons active during REM sleep. Two pathways: ->"Direct" pathway- Pons directly to spinal cord; activates inhibitory spinal cord interneurons, which inhibit motor neurons, directly inhibiting motor output during REM ->"Intermediary" pathway- Circuits to premotor neurons of the Ventromedial medulla (VMM). These VMM neurons can be excitatory or inhibitory, leading to a further two pathways: -->Excitatory pathway (Feedforward): Activates spinal cord interneurons to inhibit motor neurons -->Inhibitory pathway: Directly inhibits motor neurons

Name 5 key features of mammalian sleep. (Repetition, sensory responsiveness, motor activity, metabolism/body temp., posture, location, "sleep rebound")

-Dynamic transitions between sleep states, defined by unique brainwave patterns -Repeated on a 24-hour basis -Reduced sensory responsiveness -Reduced motor activity -Reduced metabolism/core body temp. -Adoption of a stereotyped posture -Generally occurs in a specific, protected location -Homeostatic/compensatory increase in sleep following deprivation referred to as sleep rebound

Describe the difference between dyssomnias and parasomnias

-Dyssomnias: Broad category of sleep disorders characterized by either hypersomnolence or insomnia -Parasomnias: Movements, sensations or behaviors associated with sleep, sleep stages, or partial arousals from sleep that may impair sleep maintenance

What are the cellular mechanisms that account for two forms of short-term synaptic plasticity? (The two forms, definition of short-term synaptic plasticity, location and chemical basis for the mechanism; process for the facilitation and depression outcomes)

-EITHER: An increase in strength (facilitation) or a decrease (depression) -Short term synaptic plasticity: Change in synaptic strength over the course of milliseconds to minutes -> Largely presynaptic mechanism, mostly to do w/ calcium handling in the presynaptic terminal. →Presynaptic AP enters bouton, activates Ca channels in the active zone to allow Ca influx into terminal. Can change with frequency of stimulation to modulate amount of Ca in terminal and degree of subsequent NT release ->Short-term synaptic facilitation: →Train of action potentials going into bouton causes increase in synaptic strength (increased EPSP amplitude → plateau); Associated w/ increase in presynaptic calcium ->Short-term synaptic depression: →Train of action potentials to bouton causes decrease in synaptic strength (decreased EPSP amplitude → minimum; occurs via presynaptic NT depletion

Compare and contrast declarative and non-declarative memory, give specific examples.

-Explicit (declarative): Storage and retrieval of material that is available to consciousness (what we're consciously aware of) -Implicit (nondeclarative): Storage and retrieval of skills and associations that are largely unconscious ->Different forms: priming; procedural habits; associative learning (classical and operant conditioning); nonassociative learning (habituation and sensitization) Implicit Memory Examples -Ex. of implicit memory: Pavlovian associative conditioning; brain as prediction machine- wired to predict future events ->Bell = conditioned stimulus; food = unconditioned stimulus -Another Ex: associated fear conditioning- Animal hears tone and receives temporally-linked foot shock ->Response when scared = freezing; visual output being measured →Contextual test = placed in same setting→ freezes, recognizes context and associates with the shock →Cued test = placed in modified context and hears a tone → freezes, recognizes tone and associates it with the shock -Another Ex: Non-associative learning/habituation ->Animal hears loud sound over and over; is initially startled and freezes, then is startled but doesn't freeze, eventually disregards

How is space encoded by the hippocampus? How is it measured?

-Firing of very specific regions on the hippocampus when the animal was in a very specific position (electrode recording of CA1 area of hippocampus in rat)- able to resolve single-neuron activity in the CA1; discovered firing on neurons ONLY when the animal was in a very particular point in space ->"Place cells": Hippocampal pyramidal neurons that fire preferentially when an animal is in a particular point in space (a particular 'place field') ->Thought to be a neural representation of an animal's position in space The firing of hippocampal place cells can be mapped onto space -Spike count (color-coding where firing is most robust position-wise over the total area); normalized over total time spent to create a firing rate map: "Place field" of a single hippocampal pyramidal neuron in a rat -Place fields rotate with the rotation of dominant external landmarks (i.e, rotation of the cue card being used by the rat to orient themselves in space → change in orientation of WHAT the place cell being recorded is responding to -DIFFERENT place cells are active in different parts of an environment, forming a spatial map by "tiling" overall visual space -Animals that navigate in 3D (flying)--> 3D place fields

How was the first mammalian clock gene discovered? Was it a short or long period mutant?

-Forward genetic screen; measurement of locomotor rhythms using wheel-running -Identified the first circadian clock gene ("Clock"- Circadian locomotor output cycles kaput") ->Identification of founder mouse with abnormally long rhythm; breed to get homozygous offspring →Normal: Slight leftward drifting →Heterozygous Clock mutant: Rightward drift due to longer rhythm →Homozygous: Varying degrees of arrhythmia; certain individuals had some cyclic behavior under light/dark conditions; all completely erratic under dark/dark conditions →Mutation on chromosome 5

How was the first Drosophila clock gene discovered?

-Forward genetic screens in drosophila identified first genes that were components of the "Molecular Clock" ->Forward genetic screen: Take bunch of identical organisms and mutate them, then put through a screen to identify a defect in a specific phenotype that you want to study ->Used ethyl methanesulfonate mutagenesis to randomly mutagenize a massive pool of flies then measured locomotor output with infrared light- flies put into individual tubes then subjected to infrared light directed perpendicular to the tube and hitting a detector on the opposite side. Looked for some defect in circadian behavior -Identification of the first circadian clock gene; found normal, arrhythmic, short-period, and long-period rhythms

Name 3 similarities between human narcolepsy with cataplexy and the phenotype of the Hcrt/Ox KO mouse

-Fragmented wake/sleep intervals -Reduced REM latency, as evidenced by EMG suppression -Narcolepsy results from the loss of Hcrt/Ox signaling ->Results in fragmentation and instability of sleep-wake states ->Rapid, unexpected transitions between sleep-wake states

In what region of the hypothalamus do we find neurons that are active during sleep?

-GABAergic neurons in the VLPO ->Cell bodies in the VLPO of the preoptic area in the anterior hypothalamus ->VLPO neurons are GABAergic neurons, which project to and inhibit arousal related brain regions ->Activity of VLPO neurons is associated with sleep onset

What is the role of the set point in a homeostatically regulated system?

-Homeostasis: Maintaining the stability of the internal environment ->Adjustment of variables to ensure that constant conditions are maintained in the face of external challenges ->Defending "set points" -Homeostatic control of a simple, regulated system: ->[Input -> Sensor -> Output] →Sensor connected to "error signal"; negative feedback or positive feedforward, depending on the current state of the system in relation to the set point →Define set point at this level

In encephalitis lethargica patients suffering from hypersomnia, von Economo found lesions in what brain region?

-Hypothalamus identified as critical in the regulation of sleep/wake cycles in the context of encephalitis lethargica ->Lesions found in different parts of the hypothalamus →Anterior lesions resulted in insomnia → anterior hypothalamus (preoptic area) is a "sleeping center" →Lesions of the posterior hypothalamus/midbrain resulted in hypersomnia and coma → posterior hypothalamus is a "waking center"

Describe the inter-relationships between the temporal categories of memory.

-Immediate memory: Fractions of a second-seconds -Working memory: Seconds-minutes -Long-term: Days-years

Describe Bliss and Lomo's LTP experiment (1973) (population EPSP, pathway being stimulated, basic experiment, outcomes)

-In vivo recordings from rabbit hippocampus -"Extracellular field recording" of dendrites from dentate gyrus granule cells ->Recording extracellularly, a bunch of synapses being activated together ("population EPSP")- "inward" deflection ->Extracellular EPSP generated through stimulation leading to a "Fiber volley" (whole pile of synchronous AP's), resultant downward deflection = pile of synapses being activated -Two simultaneous recordings on either side of the hippocampus (dentate gyrus); Stimulating ipsilateral perforant path pathways -Response to stimulation of the perforant path (from entorhinal cortex) -Experimental and control pathways; both recorded before and after "conditioning" (zapping experimental path with high-frequency stimulation, or "tetanus"). -Experimental and control sides of the brain ->Population EPSP recorded from either side (experimental/control paths), which is roughly equivalent. Low frequency stimulation and subsequent monitoring of EPSP's on BOTH sides →Experimental path then receives high frequency stimulation. Population EPSP on the conditioned side becomes LARGER with resumption of low-frequency stimulation; stable change in synaptic strength → long-term potentiation →Control side doesn't change

What do the dissociated SCN neuron experiments from Welsh et al, tell us about individual SCN neurons and circadian rhythms?

-Individual, dissociated SCN neurons exhibit a 24-hour period in firing rate in vitro -Process: Dissociated rat SCN neurons cultured on a multielectrode array- some will make their way to the tip of the electrodes ->Can monitor the activity patterns of the individual neurons over long periods of time- firing rate of a given neuron has a 24-hour period →Each individual cell has a ~24 period, not entrained with the other cells → endogenous rhythm ->Cells given tetrodotoxin then washed later on "picked up" where they left off, resuming their intrinsic rhythm → rhythm is somehow driven by a process occurring in the cell -Simultaneous multielectrode recording (MEA) AND calcium-imaging of SCN slice cultures: ->Calcium has its own rhythm, but phase-shifted to the left of the firing rhythm → possible mediator.

What's the evidence that NMDARs are necessary for the induction of LTP? (LTP induction dependence on depolarization, calcium influx, NMDARs; effects of hyperpolarization of postsynaptic CA1, APV, transgenic removal of NR1)

-LTP induction depends on postsynaptic depolarization to allow Mg expulsion from NMDA receptors and calcium influx into the dendritic spine of the postsynaptic neuron, ultimately leading to LTP →Blocking any part of that pathway stops LTP -Hyperpolarizing the postsynaptic CA1 neuron during synaptic stimulation prevents the induction of LTP -Synaptic stimulation in the presence of APV (competitive antagonist of NMDARs) prevents the induction of LTP -Effects of transgenic removal of NR1? ->Lack of NMDARs →Impaired LTP and spatial memory (water maze) in mice lacking NMDARs in hippocampal CA1 neurons

How was the discovery of 'silent synapses' critical to our understanding of the expression of LTP? (LTP induction --> expression and what it entails; silent synapses + definition, how they become unsilenced. Protein synthesis in LTP and anisomycin effect on it)

-LTP induction leads to "LTP expression": ->Long-term increase in synaptic strength ->Increased "sensitivity" of the postsynaptic membrane to glutamate ->Larger postsynaptic AMPAR-mediated currents -Mechanism: Silent synapses- Excitatory synapses that ONLY express postsynaptic NMDARs ->No AMPARs = No EPSC (current) at hyperpolarized membrane potentials due to Mg block Silent synapses can be unsilenced following LTP! → Current at hyperpolarized potentials -Postsynaptic AMPAR insertion accounts for LTP-induced unsilencing -NMDA receptor activation causes Ca2+ influx, which activates CaMKII and PKC, which phosphorylate many substrates, ultimately leading to the INSERTION of AMPAR's which exocytose into the postsynaptic membrane ->Protein synthesis is required for late-phase LTP (synapse growth); addition of anisomycin = early-stage induction of LTP, goes away

Compare and contrast the role of ghrelin and leptin in the regulation of appetite in the hypothalamus.

-Leptin: satiety hormone (adipose tissue); Can invade the brain through the porous parts of BB barrier and modulate excitability and gene expression of certain hypothalamic neurons -Ghrelin: hunger hormone (gut); similarly drives changes in excitability and gene expression in certain hypothalamic neurons

Define a zeitgeber and give several examples

-Light is a "zeitgeber", or "time-giver" → Any external or environmental cue (light/dark most powerful) that entrains an organism's biological rhythms to the 24-hour light/dark cycle and 12 month cycle ->Other zeitgebers: Oscillating availability of- Temperature, food, social interactions

Name 5 neurotransmitter systems that are active during wakefulness.

-Locus coeruleus of pons produces NE -Cholinergic nuclei of pons-midbrain junction (midbrain tegmentum) produces Ach -Raphe nuclei of midbrain produces serotonin -Tuberomammillary nuclei (hypothalamus) produce histamine -Lateral hypothalamus produces Orexin

Describe the ultradian pattern of EEG patterns during a night of sleep in humans. (The two basic stages of sleep; comparison of the quality of consciousness between human sleep-wake states (sensation + perception, thought, movement in each of wakefulness, NREM, and REM)

-Mammalian sleep can be sub-divided into two basic stages 1.) Non-rapid eye movement (NREM) sleep 2.) Rapid eye movement (REM) sleep →Intervals of NREM and REM during regular sleep cycle; 3-4-5 "episodes" of REM sleep cycled through over course of sleep Comparison of the quality of consciousness between human sleep-wake states -Wakefulness state: ->Sensation and perception: Vivid, externally generated ->Thought: Logical, progressive ->Movement: Continuous, voluntary -NREM Sleep: ->Sensation and perception: Dull or absent ->Thought: Logical perseverative ("thought-loops") ->Movement: Episodic, involuntary (jerk around, move, but not voluntary) -REM Sleep: ->Sensation and perception: Vivid, internally generated (mental activity during REM sleep is very similar to wakefulness) ->Thought: Illogical, bizarre ->Movement: Commanded but inhibited

Name 1 neurotransmitter system active during REM sleep.

-Midbrain tegmentum: turn on again during REM sleep

What is the effect of stimulating the medial hypothalamus vs. the lateral hypothalamus in the context of aggression?

-Stimulation of medial hypothalamus = Rage, aggressive behavior -Stimulation of lateral hypothalamus = Predatory behavior

8) Provide evidence that NPY/AgRP neurons in the hypothalamic arcuate nucleus are involved in appetite. (periventricular/arcuate nucleus location, function, and cell populations). Effect of AgRP administration, genetic destruction, AgRP levels in obese humans, optogenetic activation of AgrP.

-Periventricular nucleus (humans) or arcuate nucleus (rodents); located at the (ventral surface) bottom of the third ventricle (very bottom and sides of the third ventricle specifically) ->Critical nucleus on the ventral surface of the hypothalamus for regulating hunger; home to neuronal populations critical for feeding and satiety Arcuate cell populations: NPY/AgRP neurons project to hypothalamic areas that induce hunger behavior AgRP: Co-expressed w/ Neuropeptide Y; binds + blocks signaling through melanocortin receptors. Orexigenic, decreases metabolism -a-MSH/CART neurons project to hypothalamic areas that induce satiety behavior How do we know that NPY/AgRP neurons induce hunger? -AgRP administration (exogenous or though transgenic expression) = hyperphagia + obesity -Genetic destruction of AgRP-expressing neurons = hypophagia + leanness -Plasma levels of AgRP enhanced in obese humans -Optogenetic activation of AgRP neurons in vivo drives hyperphagia

What does the light sensitivity of rods and cones differ from melanopsin RGCs?

-Photosensitive RGC's fire action potentials when light is turned on ->Not very responsive- slow modulation of membrane potential up (when light is on) and down (when light is off); leads to delayed AP firing when light is first turned on, and persistent firing for a time after the light is turned off -Voltage clamp during increase of light intensity permits visualization of inward current development -Preferred wavelength is shifted left compared to rods and cones; just slightly more responsive to shorter wavelengths (blue range) -Intrinsically-photosensitive RGC's require much more light to be activated compared to rods and cones

Describe two ways in which LTP can be induced in a slice.

-Post-tetanus experimental pathway gains higher EPSP from basal low-frequency stimulus -LTP can also result from pairing pre- and post-synaptic activity in slices ->A normally-weak stimulus (EPSP) combined with postsynaptic depolarization results in LTP →Evidence of coincidence detection →Satisfies Hebb's postulate

Describe the pre- and postsynaptic structures of excitatory, glutamatergic synapses (structures on the presynaptic/postsynaptic sides, definition of boutons; postsynaptic specializations and dendritic spines in particular)

-Presynaptic side: Proteins specialized for regulation of NT release and regulation of released NT, cell-adhesion proteins, structural proteins which keep the synapse together, etc. -Postsynaptic side: NT receptors, including AMP and NMDA receptors; scaffolded by other structural proteins sitting in the membrane specialized for postsynaptic signaling ->Macromolecular complex in pre- and postsynaptic zones is plastic and dynamic ->Specialized for fine-tuning and regulating postsynaptic signaling Presynaptic axonal boutons (terminals): -Boutons are axonal swellings found at the site where synapses occur; release sites onto postsynaptic specializations ->Specializations can take many forms, including postsynaptic dendritic spines- often the site of glutamatergic synapses (doesn't have to be) ->Presynaptic terminal → postsynaptic spine (spines are themselves dynamic; dendrites can grow new spines or modulate their characteristics as a result of experience/activity) Dendritic spines: -Postsynaptic specializations of excitatory synapses -Get input from a single presynaptic glutamatergic terminal

What is a free-running circadian rhythm?

-Rats under conditions of constant darkness for 24 hours function under an "endogenous" rhythm → retain structure of cyclic activity/rest ->This is a true circadian rhythm or the "free-running rhythm" intrinsic to the SCN and independent of light or other zeitgebers -"Free-running" circadian rhythms gradually shift left or right in terms of the specific times cycles occur, depending on whether they are over or under 24 hours ->Introduce light exposure during the Inactive "Light" period within constant darkness = very little effect on circadian rhythm ->A light pulse during the early (active) dark phase causes a phase delay ->A light pulse during the late (active) dark phase causes a phase advance →Light exposure during a time period that "should" be dark can alter the circadian rhythm going forward

Describe the features of sleep paralysis

-Relatively common parasomnia -Waking paralysis at either of the two following times: -When falling asleep (hypnagogic) -When waking from sleep (hypnopompic) -An episode, unable to speak or move, but able to breathe and are aware -Often associated with frightening hypnagogic hallucinations -High prevalence among patients with narcolepsy and cataplexy -Apparent mismatch between REM sleep atonia (and mental state thereof) and waking

What may underlie the ability of HM to learn a skilled movement, yet have no memory of having done so?

-Retainment of Implicit memory; HM was still capable of learning a procedural/skilled movement (retained implicit memory, which doesn't require his hippocampus) -Other example: Amnesiac patients are still able to carry out a recall task following priming -Implicit memory is highly-distributed ->Priming: Neocortical function ->Procedural skills + habits: Striatum ->Associative learning: Cerebellum, Amygdala ->Nonassociative learning: Reflex pathways

What is the name of the fiber tract that extends from the eyes to the hypothalamus?

-Retinohypothalamic tract (one lane of nerve "highway"; following along optic nerve going to the brain but veering off to the SCN)

What is the effect of sleep on exchange between interstitial fluid and CSF in the brain?

-Sleep drives metabolite clearance from the adult brain -Volume of interstitial space around neurons is greater during sleep than waking ->Greater exchange between interstitial fluid and CSF during sleep than waking ->Clearance of radiolabelled amyloid-beta is twice as fast during sleep

What are 3 features that human sleep and Drosophila sleep have in common?

-Sleep is broadly defined as a state of... 1.) Behavioral quiescence 2.) Elevated arousal threshold 3.) Homeostatic regulation →All three features strongly conserved across evolution and is a near-universal phenomenon across phylogeny (but is highly variable)

Describe the circuit mediating REM atonia.

-Specific region of Pons: Sublaterodorsal nucleus (SLD); "REM-ON" excitatory neurons active during REM sleep. Two pathways: ->"Direct" pathway- Pons directly to spinal cord; activates inhibitory spinal cord interneurons, which inhibit motor neurons, directly inhibiting motor output during REM ->"Intermediary" pathway- Circuits to premotor neurons of the Ventromedial medulla (VMM). These VMM neurons can be excitatory or inhibitory, leading to a further two pathways: -->Excitatory pathway (Feedforward): Activates spinal cord interneurons to inhibit motor neurons -->Inhibitory pathway: Directly inhibits motor neurons

Describe the polysynaptic circuit in which the pineal gland is regulated by light. (Melatonin production vs. light, circuit, effect of artificial light)

-The SCN regulates melatonin production through a polysynaptic circuit -Melatonin production by the pineal gland occurs in the dark and is inversely proportional to environmental light ->Sleep-promoting hormone -Production of melatonin goes through circuit from intermediaries in hypothalamus down to sympathetic nervous system (superior cervical ganglion), ascends back to pineal gland ->Multisynaptic pathway where light influences pineal secretion of melatonin Artifici-al light: ->Phase-delays the circadian clock (later timing of circadian clock) ->Acutely suppresses melatonin →Took longer to fall asleep, reduced next-morning alertness

Describe the relationship between the hippocampus and cortical association areas in long-term storage of declarative memory.

-The hippocampus and temporal lobe is connected to broad areas of the cortex- cortical association areas: reciprocal interconnections between hippocampus, hippocampal formations, and broad areas of the cortex which control different aspects of cognitive function: visual areas, auditory, gustatory, somatosensory ->Cortical association areas thought to be location of declarative memory storage ->Reactivation of visual cortex during recall of visual images (storage site for largely-visual information) -In aggregate: Explicit long-term memory divided into facts/events- associated with function of medial temporal lobe and the hippocampus

Name 3 broad ways in which the hypothalamus controls physiology and behavior.

-The hypothalamus controls the pituitary and neuroendocrine function: -Pituitary: Structure at the bottom of the brain; anterior pituitary (adenohypophysis) and posterior pituitary (neurohypophysis) ->Hypothalamus has very specific axons descending to the pituitary- innervates specific arteries in the anterior and posterior sections of the pituitary The hypothalamus can directly modulate innate behavior and behavioral state: -Hypothalamic modulation of attention, cognition, emotion, motivation, and reward ->Occurs via diverse, extensive projections throughout the brain

What is the role of the medial entorhinal cortex in representing space?

-The medial entorhinal cortex (the input to the hippocampus) has "Grid" cells -When an animal is navigating a space, entorhinal cortical grid cells fire at multiple locations in space, corresponding to a regularly-spaced grid-like pattern of signal "clusters" ->Represent local space as a Euclidean map; provides a means of navigation in an environment ->Nearby grid cells have similar spacing and orientation, but are out of phase with one another ->Spacing increases along the dorso-ventral axis of the medial entorhinal cortex →Dorsal grid cells: close spacing →Ventral grid cells: wider spacing

What is unique about RGCs that project to the hypothalamus as opposed to ones that project to the visual thalamus?

-Vast majority of RGC's of the image-forming retina are NOT photosensitive; small population of very specialized RGC specially-tuned to connect with the SCN of the hypothalamus and detect environmental light and dark ->Majority of RGC's are tuned for vision and go to the visual thalamus

Describe the synaptic homeostasis hypothesis of sleep.

-Wakefulness is associated with synaptic potentiation ->From experience-dependent plasticity ->Saturates and is metabolically expensive -Sleep (Slow wave sleep specifically) is associated with synaptic depression ->Renormalizes synapses Maintains optimal network plasticity

EEG characteristics of wakefulness, NREM (stage I-IV), and REM

-Wakefulness: Low amplitude, high frequency; cortical desynchronization. Dominated by beta waves (13-30 Hz) -NREM: ->Stage I: Transitional stage; start seeing invasion of Theta waves (3-7 Hz) and Alpha waves (8-12 Hz) ->Stage II: Resembles stage I, but see larger amplitudes and slower events. Specific signatures: "sleep spindles"- high-frequency buzzes (12-14Hz), and K-complexes ->Stage IV: High amplitude, low frequency; synchronized; delta waves (0.5-2Hz) -REM: ->Low voltage ("wake-like"), desynchronized; theta waves (3-7 Hz)

Describe 6 critical functions of the hypothalamus.

1.) Blood pressure and electrolyte composition -Thirst -Salt appetite -Drinking behavior -Autonomic control of vasomotor tone (constriction and dilation of blood vessels) 2.) Core body temperature -Core body temp -Autonomic control of body heat conservation and body heat dissipation -Thermoregulatory behavior (seeking warmth or coolness) -Hormone secretion that influences metabolic rate 3.) Arousal and sleep-wake cycle -Circadian clock: Controlled by superchiasmatic nucleus of the hypothalamus; -Response to the 24 hr cycle of light and dark -Arousal (active mechanisms of wakefulness) -Sleep (active mechanisms of sleep) 4.) Feeding and energy metabolism -Hunger and feeding behavior (active mechanisms for hunger) -Satiety and satiety behavior (active mechanisms for satiety) -Body weight -Autonomic control of digestion -Autonomic control of metabolism 5.) Reproductive/sexual behavior -Reproductive/sexual behavior -Neuroendocrine regulation of reproductive physiology (menstrual cycles, lactation, etc.) -Autonomic regulation of reproductive organs -Maternal/paternal behavior (nesting, bonding, caretaking, etc.) 6.) Defensive/aggressive behavior -Autonomic control of fight or flight responses -Neuroendocrine and autonomic control of stress responses ->Paraventricular nucleus regulates stress responses and communicates with pituitary and adrenal glands -Defensive behavior (against predator) -Aggressive behavior (against rival) -Predatory behavior (food-seeking)

What is the tetrad of narcolepsy?

1.) Excessive daytime sleepiness 2.) Sleep paralysis (paralysis during sleep-to-wake or wake-to-sleep transitions 3.) Cataplexy (sudden muscle weakness during wakefulness 4.) Hypnogogic hallucinations (vivid, dream-like hallucinations while dozing)

Explain Hebb's postulate (1949) and its impact on the cellular basis of learning and memory in the brain.

Hebb's postulate: If cell A repeatedly excites cell B, some growth process/metabolic change takes place in one or both cells such that A's efficiency as one of the cells firing B is increased -Synaptic plasticity: A change in synaptic strength ->Shapes communication between neurons by altering the strength of synaptic transmission ->Synaptic plasticity is required during neural development so that stable and appropriate connections can be made ->Required for experience-dependent modification that underlies learning and memory ->Takes many forms, in many different neurons and circuits, from nematodes to humans ->Synaptic plasticity can be short or long-term

What is the evidence that forms of non-declarative memory depend on the striatum?

Learning predictive relationships involves the striatum/basal ganglia: -Study: Amnesiac and Parkinson's patients had to perform a task -Predication task and declarative memory task aspects ->Amnesiac patients performed poorly on declarative memory task but reasonably well on the prediction task (only minor impairment) ->Parkinson's patients performed perfectly on the declarative task, but poorly on the prediction task -Other study: Parkinson's patients on L-DOPA (first-line treatment for classical parkinson's disease) performed much better on a prediction task ->Suggests striatum/basal ganglia is involved in implicit memory performance

How are NMDARs like coincidence detectors?

NMDARs have a magnesium binding site; at hyperpolarized membrane potentials, Mg sits in pore and requires depolarization of the membrane potential to unplug and permit inward current flow →NMDARs are thus a "coincidence detector" of pre- and postsynaptic activity, requiring BOTH depolarization AND glutamate simultaneously; output reflects those two things occurring simultaneously →Monitor of presynaptic activity (glutamate) and postsynaptic activity (depolarization) -AMPA and NMDA receptors typically co-exist at postsynaptic sites

NREM sleep vs. REM sleep (Paralysis, characteristic waves, dreams, etc.)

NREM Sleep: "Slow-wave sleep" (SWS): -Deepest stage of sleep- highest arousal threshold (hardest to be woken up from) -No muscle paralysis, some episodic, involuntary movement -Characterized by slow delta waves, which dominate the EEG (0.5-2 Hz) ->Low frequency, high amplitude waves ->Reflects slow, synchronous cortical activity -Mental activity: ->NREM sleep is less associated with dreaming than REM sleep ->Dreams during NREM sleep are less vivid, less narrative, less emotional, and less memorable upon waking ->Sleep-walking, sleep-talking, night terrors, etc. (parasomnias) mostly occur during NREM sleep -REM sleep: ->"Paradoxical sleep" (PS) -->Because of the "wake-like" EEG pattern, reflecting high cortical activity ->Almost complete muscle paralysis (REM atonia) ->Rapid, random eye movements ->Characterized by: -->High-frequency, low amplitude waves -->Theta component ->REM episodes occur ~4-5 time/night ->Increasing duration of REM episodes late in the night -Mental activity REM sleep is most associated with dreaming -Dreams during REM sleep are vivid, detailed, prolonged, narrative, emotion-laden, and more memorable upon awaking

Describe Patient HM's memory deficits. What functions were spared? What does the case of Patient HM teach us about the nature of memory?

Patient HM: Bilateral medial temporal lobe resection- medial temporal lobe scooped out, including: ->Hippocampal formation ->Entorhinal cortex ->Parahippocampal gyrus ->Amygdala ->Parts of association area of the temporal cortex -Effects: Experienced devastating anterograde amnesia: he could not form new memories ->Memory span of ~20 seconds -Remarkably specific deficits: ->Normal short-term memory ->Normal retrograde long-term memory (childhood) (somewhat hazy) ->Normal semantic memory ->Normal IQ, personality, social perception, etc. -The nature of memory: HM = First clear anatomical link between the medial temporal lobe (including the hippocampus and parahippocampal gyrus) and memory ->Resection spared working memory but impaired transfer of new memories into long-term memory

How has a postsynaptic Ca2+ rise been proposed to be linked to AMPAR insertion or internalization in LTP and LTD respectively?

Postsynaptic AMPAR insertion accounts for LTP-induced unsilencing -NMDA receptor activation causes Ca2+ influx, which activates CaMKII (Ser/Thr protein kinase) and PKC, which phosphorylate many substrates, ultimately leading to the INSERTION of AMPAR's which exocytose into the postsynaptic membrane Signaling mechanism underlying SC → CA1 LTD -Calcium entering synapse through NMDA receptors activate protein phosphatases, which dephosphorylate substrates → leads to internalization of AMPA receptors (back to "reserves") ->Mutant phosphatase = impaired spatial memory; LTD contributes to behavioral flexibility →Both processes rely on NMDARs mediating Calcium influx, but diverge from there

What is the role of priming in implicit memory?

Priming in implicit memory: ->Subject given set of words to read (is "primed" with those words), then is prompted to complete a set of word stems, some of which are from the list of "priming" words; more readily completes those stems with the words from the original list ->Fallibility: The generation of FALSE memories, such as a list of words being memorized which is associated with a similar word that is created as a false member of that list (i.e, pie, sugar →"sweet") Examples: -Procedural (skills and habits) -Associative learning -Motivation and memory: Role of hunger state when recalling images of food and non-food images ->When hungry, you more readily remember imagery associated with food

What is the difference between an actogram and periodogram?

Rats entrained to a light/dark cycle of 24 hours (12:12) → actogram activity reflects periods of wakefulness and sleep "Periodogram" developed from data to give peak power → "Period" of data (in the 12:12 case, 24-hour period)

Name 5 long-term effects of sleep deprivation in humans.

Short-term effects: -Diminished motor performance -Impaired cognitive performance (confusion, memory loss, etc.) -Headache, malaise -Depression -Impaired IS Long-term: -Stroke -Obesity -Heart attack -Cognitive impairment -Neural degeneration

What is the difference between homeostatic and circadian sleep patterns? Define sleep pressure

Sleep is regulated by both circadian and homeostatic sleep drive: -Two circadian cycles of being awake and asleep ->Circadian cycle of alertness driven by circadian information- sinusoidal wave of alertness over time (starts lower, peaks, decreases) →Throughout the alertness cycle, the Homeostatic "sleep drive" constantly builds up over time, diminishing when we sleep ->Area between the two curves = "Sleep pressure"; very low just after waking, grows over the course of the day -Adenosine is the best candidate for the homeostatic sleep factor ->Produced by the break up of ATP during energy expenditure and builds up in the brain during wakefulness and is diminished during sleep

Name five differences between Bliss and Lomo's LTP experiment and classic SC → CA1 hippocampal pyramidal cell LTP in slices (trisynaptic circuit vs. Schaffer collateral pathway)

The hippocampus structure: Trisynaptic circuit -ALL excitatory (glutamatergic) synapses -Perforant path from entorhinal cortex (entry point); synapse on granule cells in the dentate gyrus, which send axons to region CA3; CA3 (pyramidal cells) → CA1 (pyramidal cells), which is an output of the hippocampus to the subiculum Bliss + Lomo experiment: -In vivo recordings from rabbit hippocampus -Extracellular field recording from dentate gyrus cells = EPSP is recorded as a downward deflection -Response to stimulation of the perforant path (from the entorhinal cortex) and recording of a "population EPSP" resultant of many synapses stimulated at once -Simultaneous recordings of two sides of the dentate gyrus (Experimental/Control) after stimulating the two ipsilateral perforant pathways -Basal conditions: low-frequency stimulation, corresponding to roughly equal EPSP's between the two pathways ->Experimental pathway tetanized w/ high-frequency stimulation →Low frequency stimulation thereafter elicits persistently-stronger EPSP in the Experimental pathway The Hippocampal slice -Instead of Peforant path, the typical pathway studied in slices is the Schaffer collateral pathway (CA3 -> CA1); utilize parallel axons as control/experimental groups ->Same capacity for tetanus-induced LTP