Neuro 4: Hypothalamus + Sleep

Sleep + Memory Storage

- "Reactivation" + transfer of memory to cortex has another important consequence: - *frees up "hippocampal storage space"* for the next day's learning - so we also learn better after sleeping (significantly enhanced even after a 90 minute nap)

Leptin

- *cytokine* produced by adipose tissue - binds to Ob receptors in arcuate nucleus, signaling hypothal to orchestrate a series of behavioral, metabolic, and neuroendocrine adaptations: 1) During nutrient abundance: secretion increased --> decreased appetite, increased caloric disposal 2) When nutrients insufficient: secretion declines --> increased appetite, energy conservation, behavioral arousal, metabolic adaptation

Middle (Tuberal) Region

- *directly above pituitary* + infundibulum - subdivided into *dorsomedial + ventromedial nuclei* (while lateral nucleus is continuous w/ both rostral + caudal levels) - participate in many different hypothalamic functions - receive input from limbic and visceral sensory structures (solitary nucleus) - *arcuate nucleus* sits in floor of infundibular recess (Like periventricular nucleus, releases factors into hypophyseal portal system that promote or inhibit release of ant pituitary hormones)

Hypothalamus location

- 3D reconstruction of hypothalamus (in yellow) - its many nuclei line walls of anterior third ventricle

Producing awake state

- Activation of *cholinergic, monoamine + histamine* - containing networks together produces awake state!

"activating" function of the RF

- Signals from all kinds of receptors can influence RF neurons b/c 2nd order sensory neurons on way to thalamus send collaterals to RF - When sensory receptor is stim'd (visual, vestibular, auditory, pain, temp), signals reach cortical areas + also reach RF! - Thus, under normal conditions, are always signals coming into RF --> *state of tonic activity* - Consistent w/ its role in mediating general arousal

Neural circuits governing sleep

- Sleep is NOT simple decrease in brain activity - brain is actually more active during REM sleep - Sleep: series of precisely controlled brain states, sequence *controlled by brainstem nuclei* that project throughout brain - Neuronal circuits responsible for sleep and transition b/t stages complex!

Reticular Formation (RF)

- complicated network of circuits in core of brain stem - Extends from lower medulla to upper midbrain, where it fuses w/ thalamic cell groups - Consists of clusters of neurons that fill territories not used by CN nuclei, pontine nuclei or fiber tracts - *Serotonin* (raphe), *NE* neurons (locus coeruleus), *DA* neurons (SN + VTA) part of it! - neurons have extensive interconnections w/ forebrain + spinal cord neurons - role in many *global functions*

Zones of hypothalamus (rostral-caudal)

- contain discrete nuclei w/ different functions 1) most anterior zone: - "preoptic" region (spills rostrally over optic chiasm) - Behind sits "supraoptic" region (directly above chiasm) 2) middle = "tuberal" region 3) "posterior hypothalamus"

Seasonal affective disorder (SAD)

- depression during winter - long winter nights = greater risk - Women affected more - A less common form involves summer depression - Symptoms: include increased appetite with weight gain, increased sleep and daytime sleepiness (other forms of depression, weight loss /decreased sleep more common); less energy, loss of interest in /activities, social withdrawal - Cause: Unclear, seasonal variations in light exposure + melatonin levels. treatment: bright light (30-60 min/day), SSRI's + therapy - Support for "insufficient light" theory: Prevalence of SAD ~1.5 percent in Florida, ~9 percent in northern US, 9.5% in Finland - low in Iceland (diet protective?)

anterior pituitary (adeno-hypophysis)

- derived from *pharyngeal ectoderm (Rathke's pouch)* - contains glandular cells that secrete hormones into circulation - secretion is controlled by releasing factors from small (parvocellular) hypothalamic neurons from *arcuate, medial preoptic, periventricular + parvocellular portions of paraventricular nuclei* - neurons project to median eminence --> portal system of fenestrated capillaries - these factors (*all peptides, except for DA*) diffuse out of caps, act on secretory cells in anterior pituitary, affect hormone release

poikilothermia

- elimination of all temperature regulation - can occur from lesion in posterior hypothalamus (which contains fibers of passage from anterior hypothalamus, which controls heat dissipation)

Reticular Formation pic

- everything thats NOT something else! (serotonin, DA neurons)

Hypothalamic Functions

- four major roles, mnemonic = HEAL 1) *Homeostasis*: orchestrates neurohormonal control over hunger, thirst, temperature, stress, sleep, reproduction & other behaviors 2) *Endocrine*: exerts master control via pituitary 3) *Autonomic*: central controller of both sympathetic + parasympathetic nervous systems 4) *Limbic*: integral part of emotion circuitry of brain

Thalamocortical neurons

- have 2 modes of firing: 1) oscillatory or bursting 2) tonically active - oscillatory state --> tonically active state by activity in cholinergic nuclei of the pons-midbrain junction - When cholinergic neurons are active (wakefulness + REM), thalamocortical neurons enter tonically active mode - When cholinergic neurons inhibited (non-REM sleep), thalamocortical neurons are in the "disconnected" oscillatory mode

Consequences of sleep deprivation in humans

- Average sleep length in humans varies considerably - getting too little sleep creates a "sleep debt" that must be repaid - before repayment, judgment, reaction time, memory, other cognitive functions impaired - if deprivation persists, moods swings + hallucinations - record for voluntary sleeplessness in humans is 19 days - *Fatal familial insomnia*: genetic, onset middle age: hallucinations, seizures, loss of motor control, inability to enter deep sleep. Patients die w/in several years of onset

supraoptic + paraventricular nuclei

- home to large neurosecretory (*magnocellular*) neurons - project axons thru infundibulum to post pituitary, where hormones are released - contain *9-amino-acid hormones* 1) oxytocin + 2) vasopressin/ADH - Individual neurons produce only one hormone, though both hormones are produced in both nuclei 1) Vasopression increases reabsorption of water in kidney, thereby decreasing urine production 2) Oxytocin triggers contraction of uterine + mammary smooth muscle, important in parturition, milk ejection, affiliative emotions

Gut peptides

- hormones that influence appetite 1) *Ghrelin* = adipogenic hormone secreted by empty stomach that *promotes appetite* via receptors in arcuate + lateral nuclei 2) *Insulin* secreted during mental anticipation of meals + continues during food digestion and absorption, when it *decreases appetite* - enter brain + influence appetite, energy utilization, conditioned feeding through action on hypothal, nucleus accumbens + other limbic structures

mammillothalamic tract

- hypothalamic efferent tract - connects mammillary bodies to anterior nucleus of thalamus - part of *Papez' circuit /limbic loop*

satiety center

- in (ventro)medial hypothalamus - *lesions* here cause *overeating + obesity*

Histamine-containing neurons

- in tuberomammillary nucleus (TMN) of hypothalamus - why antihistamines make you sleepy - like NE + serotonin neurons, histamine neurons project widely throughout brain

Lateral Hypothalamus + MFB

- interspersed w/ longitudinally running *medial forebrain bundle (MFB)* - MFB = bidirectional pathway projecting from midbrain tegmentum, through hypothalamus, to *forebrain septal area*

INAH-3

- interstitial nucleus of anterior hypothalamus - tiny subnucleus in medial preoptic hypothalamus - twice as large in men as in women

medial preoptic hypothalamus (MPOA)

- key role in temp regulation, + reproductive physiology /behavior - controls release of *GnRH*, contains a high density of *estrogen receptors* - is site of best-described sexual dimorphism in brain: tiny subnucleus, *INAH-3* ("interstitial nucleus of anterior hypothalamus") - is rostral continuation of medial hypothalamic areas

tuberomammillary nucleus

- located in post hypothalamus - contains *brain's only histaminergic neurons* - project widely to: reticular formation, thalamus + cortex - active during awake state, quiescent during sleep, form part of *ascending arousal system* - Anti-histamines cause drowsiness

Papez' circuit /limbic loop

- mammillothalamic tract of hypothalamus is part of it - connects cingulate gyrus, hippocampus + hypothalamus - is thought to participate in memory storage

Tonic activity of thalamocortical neurons

- mode where information is being transmitted to cortex that is correlated with incoming stimuli (from RF) - occurs during wakefulness + REM sleep (desynchronized EEG) - when info is actually being transmitted

Oscillatory thalamocortical firing

- mode where thalamic + cortical neurons show synchronized activity - meaningless feed-forward loop "disconnecting" cortex from outside world - maximal during non-REM sleep (lowest freq, highest amp EEG waves) - reflecting oscillatory firing of cortical neurons (synchronized EEG) - important for memory consolidation

Preoptic (anterior) region

- most rostral level of hypothalamus lies above + anterior to optic chiasm - Another landmark = anterior commissure - black stippling = MFB

Diabetes insipidis (DI)

- much less common than mellitus + more dangerous - characterized by an increased production of urine (*polyuria*) and excessive thirst and drinking (*polydipsia*) - can be caused by tumors or fractures at base of brain which affect *supraoptic nucleus, hypothalamo-hypophyseal tract, or pituitary* - Such causes classify DI as "*neurogenic*," distinct from nephrogenic causes that may involve insensitivity to vasopressin - patients can urinate up to 20 L/day!

posterior pituitary (neuro-hypophysis)

- neural structure derived from evagination of embryonic ventricular system floor - *does not contain glandular cells* - contains terminals of magnocellular neurons from paraventricular and supraoptic nuclei - these terminals *secrete oxytocin + vasopressin directly into capillary bed*

Modafinil

- new wakefulness-promoting drug (FDA approved for narcolepsy, shift work sleep disorder and excessive daytime sleepiness associated with obstructive sleep apnea) - acts by stimulating orexin neurons (not proven) - Probably several mechanisms of action, including blocking reuptake of DA + norepinephrine, perhaps increasing histamine release

mammillary bodies

- nuclei: most distinguishing feature of post hypothalamus - do not interface w/ pituitary, form virtually *no connections to other hypothalamic nuclei* - function in *limbic system*, receiving input from hippocampus, send output to anterior thalamus - *Damage impairs memory*

Dreams

- occur primarily in REM (elaborate, vivid, hallucinogenic, emotional), - Non-REM: fewer, shorter, more conceptual, less vivid, less emotional - purpose unknown, but are important! - Occurs in all mammals (and some birds) - REM-sleep deprivation leads to *REM rebound* - will make up for loss naturally - Much more difficult to prevent REM sleep than other forms of sleep in sleep lab studies

Median eminence

- one of 7 *CVOs* (circumventricular organs) that has a leaky vasculature - Axons from neurons in arcuate, periventricular, paraventricular + medial preoptic nuclei release releasing/ inhibitory factors here - which then enter *upper capillary bed* of pituitary portal system + flow down to ant pituitary - OT= optic tract

Autonomic Hypothalamic Efferents

- originate in paraventricular nucleus - descending projections to pregang symp neurons in intermediolateral cell column - control pupillary dilation (damage above T2 causes constricted, barely responsive pupils - ipsilateral)

Circadian Rhythms

- periodicity of ~24 hrs - *internal clock* - generated by *pacemaker activity of cells in SCN* - Pacemaker activity *intrinsic* to SCN cells (when grown in culture, continue to exhibit circadian rhythms!) - evolved to maintain appropriate periods of sleep + wakefulness in spite of variable amounts of daylight + darkness in dif seasons + parts of planet

Cholinergic neurons pic

- pontine reticular formation - desynchronized eeg (like during REM) means you are moving stuff!

lateral nucleus

- present at all rostrocadual levels, including posterior hypothalamus - functions as rostral *extension of midbrain reticular formation* - involved in arousal, attention, feeding, and reproductive behaviors

Hypothal afferents from brainstem

- sensory input from PAG, reticular formation, solitary nucleus - ascend in: 1) *dorsal longitidunal fasciulus* (dorsal brainstem near 4th ventricle) 2) *medial forebrain bundle, MFB* (fibers cont rostrally in lateral nucleus of hypothalamus) - provides modular input from various monoaminergic cell groups in brainstem to all of forebrain

Mid-sagittal view of hypothalamus

- sits in lateral walls of inferior third ventricle, extending from lamina terminalis to hypothalamic sulcus

Memory consolidation

- slow wave sleep: newly encoded info repeatedly reactivated (same cells fire) - triggered by interactions b/t cortex + hippocampus - Reactivations help *transfer memory to neocortex*, site of long-term storage + integration w/ other memories - we perform better when tested after night of sleep

retinohypothalamic tract

- specific ganglion cells in retina that are depolarized by light + send axons to SCN - allows SCN to detect decreased light as night approaches, to synchronize physiological processes w/ day-night cycle

Ghrelin

- the *hunger hormone* - *adipogenic* hormone secreted by empty stomach - promotes appetite via receptors in *arcuate + lateral nuclei*

Sleep & wakefulness

1) *tuberomammillary nucleus* 2) *lateral posterior hypothalamus* produces *orexins (active in waking state)* neurons project widely to thalamus, basal forebrain, tuberomammillary nucleus, cholinergic + adrenergic neurons in rostral pontine reticular formation 3) *ventrolateral preoptic nucleus (VLPO)* produces *GABA (active in non-REM sleep)* - inhibit tuberomam + cholinergic neurons in reticular formation

Drugs that affect sleep

1) Benzodiazepines (*enhance GABA* transmission): decrease time to onset of deep sleep 2) Antihistamines (*block histamine* transmission): promote sleep 3) Amphetamines (*increase monoamine* transmission): promote wakefulness 4) Modafanil (amphetamine-like actions that *increase monoamine*, histamine or orexin): promotes wakefulness 5) Caffeine (*adenosine receptor antagonist*): promotes wakefulness

Renin + ADH

1) Renin (made in kidney) catalyzes conversion of Angiotensin I (in lung) to Angiotensin II, which travels through plasma to subfornical organ, triggers release of ADH 2) ADH promotes: increased Na resorption, increased heart contractility, increased BP - Sweating can reduce BV by 1-2%, activating baroreceptors + also increasing osmolality

Memories: slow-wave + REM sleep

1) Slow-wave sleep: Initial consolidation/ transfer to cortex 2) REM sleep: Integrative stage of memory processing beyond consolidation (synaptic strengthening via LTP in cortex) - *Unitization* (867-5309 .... 8675309) - *Assimilation* (new memories into pre-existing networks of related info: recognizing relationships b/t words) - *Abstraction* - eg discovering hidden rule for solving class of math problems - May explain evolution of *sequential SWS-REM cycles* across night - whole process may be optimized by multiple SWS-REM cycles (within a night + over several nights)

Hypothalamic Nuclei: medial

1) anterior: paraventricular (PV), anterior (A), suprachiasmatic (S) 2) tuberal/middle: dorsomedial (DM), ventromedial (VM) and arcuate (ARC) 3) posterior: mammillary (M) and posterior nuclei (P)

Hypothalamis-pituitary connections

1) direct neural connections to neurohypophysis (where hypothal neurons release oxytocin +vasopression 2) hormonal secretion into hypophyseal portal system (carries hypothalamic releasing + inhibiting factors to adenohypophysis, modulate release of various pituitary hormones)

Hypothalamic tracts + nuclei - anatomy

1) fornix: pierces hypothalamus + terminates in right mammillary body - *divides hypothalamus into medial + lateral zones* - provides bidirectional input b/t hypothal + hippocampus, producing changes in endocrine + ANS activity as dictated by internal drives and emotional experience 2) mammillothalamic tract (prominent mammillary bodies to anterior nucleus of thalamus)

Functional importance of REM sleep

1) integrates memories (probably) 2) *Francis Crick theory*: Neuronal activity during REM serves to *unlearn* - degrades rather than enhances info content - inappropriate or accidental connections may be weakened by random activation of synapses during REM sleep (*LTD?*) 3) maybe, minimal role for REM (*MAO inhibitors eliminate REM but no ill effects*)

Hypothalamic Afferents

1) sensory from PAG, reticular formation, solitary nucleus (ascend dorsal long fasc + MFB) 2) sensory from *optic nerve* (small set of retinal ganglion cells directly to SCN) 3) from limbic structures (fornix, stria terminalis, ventral amygdalofusal)

Supraoptic (anterior) hypothalamus

1) suprachiasmatic nucleus (SCN) - controls circadian rhythms 2) Large neurosecretory ("magnocellular") neurons in *supraoptic + paraventricular nuclei* (oxytocin, vasopressin/ADH) 3) *parA*ventricular nucleus (source of descending autonomic fibers) 4) *perI*ventricular nucleus (lines 3rd ventricle, produces releasing factors that circulate in portal system to *control ant pit*)

Hypothalamic Efferents

1) to hippocampus via fornix 2) to autonomic brainstem structures (DLF, MFB and mammillotegmental tracts) 3) to amygdala, bidirectional (stria terminalis + ventral amygdalofugal pathway) 4) to cortical, medial forebrain areas (including septal nuclei + orbitofrontal cortex) 5) mammillothalamic tract (*Papez circuit*) 6) direct connections to neurohypophysis (oxytocin/vasopressin release) 7) hormones to portal system (releasing/inhibiting factors to modify pituitary)

Pituitary adenomas

Cortisol and aldosterone increase blood pressure, electrolyte balance, increase blood glucose

HPA axis + depression

- Cortisol levels: peak at waking, decline through day - CRH produced in paraventricular nucleus - Hippocampal pyramidal neurons have high levels of glucocorticoid receptors, project to PVN to regulate CRH production - depression: *hippocampus atrophied, negative feedback impaired* --> *surplus CRH*, ACTH, cortisol secretion - CRH neurons send branches to midbrain, where they *inhibit dopamine- and serotonin-releasing neurons*, so excess CRH in depression may reduce levels! - *Dexamethasone suppression test* (tests for hypercorticosolemia /Cushing disease) also used in diagnosing depression

REM sleep

- EEG during REM is similar to awake state + stage I of non-REM sleep - Thus, known as *paradoxical /desynchronized sleep* - characterized by *dreaming* - Many neurons are as active in REM as during wakefulness. Some are more active, e.g., neurons that generate rapid eye movements

Stages of Sleep

- Humans cycle between 2 types of sleep: rapid eye movement (REM) sleep + non-REM sleep. These are distinguished using: 1) *Electroencephalography* (EEG) - most important method - electrodes applied to standard positions on scalp, measures electrical activity in brain regions (low spatial resolution ~4cm) 2) *Electrooculogram* (EOG) - monitors eye movement 3) *Electromyogram* (EMG) - monitors muscle tone

Physiology of REM sleep

- Increased BP, HR + metabolism (almost as high as awake state) - Rapid, rolling eye movements - Atonia in muscle groups of limbs, trunk, + neck - (GABA activity in pontine reticular formation inhibits LMN) - inactive muscles = motor response to dreams relatively minor (*sleepwalking =non-REM sleep*, not associated w/ dreams) - Signs of sexual arousal - *Active brain in inactive body*

Cholinergic neurons near pons-midbrain junction

- Key component of what was originally termed ARAS - Active during wakefulness/REM, quiet during non-REM sleep - Produce arousal via projections to thalamic nuclei, which project widely throughout cortex + increase its general activity (related to arousal + attention). - Activation of thalamo-cortical neurons responsible for de-synchronization of EEG during wakefulness + REM sleep

photoentrainment

- Light entrains circadian rhythms to the day-night cycle

Monoamine neurons

- NE neurons of locus coeruleus - serotonin neurons of raphe nuclei - DA neurons do *not* display changes in firing during sleep/wake cycle (might play a role: *Modafinil*)

orexin!

- Neurons of lateral hypothalamic area contain *neuropeptide* orexin (*hypocretin*) - Orexin neurons have widespread projections, generally *excitatory* - An important function of orexin neurons is to *activate histamine + monoamine neurons* that promote wakefulness - There is great interest in developing drugs that activate orexin neurons and thus promote wakefulness

REM sleep in infants

- New born infants: 8 hrs of REM sleep per day (2 hr in adult) - Special sleep cycle, periods of 50-60 min of sleep, *starting from REM* - Infants born prematurely: even more time spent in REM - REM "exercises" the developing nervous system?

So, is sleep just the absence of input to the RF?

- No - stimulating other parts of RF, or stimulating brain regions outside RF produces sleep. - This was important for demonstrating that sleep is an active process. Up till the 1950's, scientists thought sleep was passive decrease in brain activity (decreased sensory input resulted in decreased RF activity, which resulted in decreased cortical activity, and ultimately in sleep)

Melatonin

- SCN also regulates activity of pineal gland (*multi-synaptic pathway*) - pineal gland synthesizes melatonin, secretes it into bloodstream - interacts w/ *melatonin receptors on SCN neurons* that in turn influence sleep-wake cycle - synthesis increases as light decreases, reaching its maximal level between 2 and 4 am - In elderly: *produces less melatonin* -may explain why older people sleep less + are more often afflicted w/ insomnia

Current Leading Sleep Theory

- Sleep is involved in *offline processing/ consolidation of recently acquired memories* 1) *Encoding*: Initial learning process (awake state) 2) *Consolidation*: Process that transforms new and initially labile memories into more stable representations, integrated into network of pre-existing long-term memories - Sleep facilitates *consolidation of newly formed episodic memories* - Memories stabilized (more resistant to interference), performance in memory tests improved - Consolidation involves *"reactivation" of memories* - If "reactivation" occurred during wakefulness, it would presumably disrupt "encoding" of new memories

Physiology of non-REM sleep

- Slow rolling eye movements - Decreased muscle tone, heart rate, breathing, BP, metabolic rate and temp - body movements reduced compared to wakefulness, but common to toss + turn - *Inactive brain in an active body*

Control of temperature

- Temp-sensitive neurons found throughout, but ant hypothal (medial preoptic area *MPOA) = most important zone for thermoregulation* - Pyrogens access MPOA vasculature via OVLT, trigger production of *prostoglandin E2 (PGE-2) in cap endothelia* - PGE2 upregulates "set point" of temperature-controlling neurons in MPOA, triggering *fever*: cascade of heat-producing processes (shivering, cessation of sweating, vasoconstriction) - NSAIDs (aspirin, ibuprofen) reduce fever by *inhibiting COX-2, thereby preventing PGE-2 synthesis + reducing "set point" of MPOA neurons*

SCN regulation of sleep timing

- To synchronize physiological processes with the day-night cycle, SCN must detect decreased light as night approaches - receives this info via *retinohypothalamic tract* - Thus, light "entrains" natural rhythms of SCN to day-night cycle - Projections from SCN regulate rhythms of sleep + other functions - SCN *regulates timing of sleep but not responsible for sleep itself* - Animals w/ SCN lesions no circadian pattern, but sleep normal total amount of time each 24 hr period

Sleep + Age

- Total sleep time declines progressively until age 20-25, then plateaus. - REM sleep very high in infants/ children, then plateaus 20-60, drops off again late in life - *Stage 4 sleep: dramatic decline* with aging. diminished restful properties of sleep, higher frequency of spontaneous awakening

Circumventricular organs

- Two located near anterior hypothal: 1) *subfornical organ (SFO)* 2) *organ vasculosum of lamina terminalis (OVLT)* - regions with "leaky" vasculature, just like in periphery, so they are *in chemical communication w/ plasma* - Tanycytes prevent substances in CVO from accessing rest of brain + ventricles

Non-REM sleep stages

- Waking (eyes open) - high freq, low amp activity (*beta activity*) 1) transition to sleep, several min. EEG shows *low-amp, mixed freq* pattern. amp slightly greater, freq slightly decreased (compared to waking) (*theta waves*) 2) light sleep, further decrease in freq + increase in amp of EEG waves,intermittent bursts of sinusoidal waves called *sleep spindles* (last 1-2 min) 3) Moderate to deep sleep, # spindles decreases, amp of low-freq waves increases still more 4) predominant EEG activity = high-amp, slow waves, *delta waves* - reflect synchronized electrical activity of cortical neurons - III + IV together = *slow-wave sleep* (deepest, most difficult to awaken) - After period of slow-wave sleep, *sequence reverses* + REM sleep may begin

Memory encoding

- Waking brain: initial encoding primarily in hippocampus (cortex also involved) associated w/ activity in specific neurons (in sequence) - during sleep, same cells fire again!

Feeding Center

- aka *lateral hypothalamus* - *lesions here cause weight loss* - Some of its neurons secrete orexin, which acts elsewhere in brain to increase feeding - lateral nucleus runs through all rostro-caudal levels of hypothal, continuous w/ midbrain tegmentum

normal state (no fever)

- anterior hypothalamus promotes heat-loss, lesions here lead to *hyperthermia*! - posterior hypothalamus = *heat conservation* - Bilateral posterior lesions lead to poikilothermia b/c of loss of both heat-conserving neurons + descending heat-dissipating pathways from ant hypothal - Steroid hormones *(test +estrogen) modify set point* of anterior hypothal neurons

Pyrogens

- bacterial toxins, such as lipopolysaccharides (LPS) - endogenous cytokines, such as interleukin-1b (IL-1b) or NE from solitary nucleus - induce cyclooxygenase-2 (COX-2) gene in capillary endothelia - COX-2 liberates PGE2, which activates heat-production mechanisms in MPOA

suprachiasmatic nucleus (SCN)

- tiny nucleus, (less than 10,000 neurons) - acts as body's *"master clock"* controlling circadian rhythms - free-running period ~ 25 hours, entrained by light, locking it to actual day length - Visual input comes directly from small # of retinal ganglion cells that project through the optic nerves/chiasm - sits immediately above optic chiasm! - neurons also express *melatonin receptors*, nighttime rise in secretion by pineal gland helps entrain circadian clock - controls *daily fluctuations* in temp, BP, metabolism, cortisol (+ other hormone) secretion, arousal

hypothal: Coronal section - tuberal & posterior level

- view of tuberal level (fattest) 1: anterior commissure 2: optic tract 3: third ventricle 4: basal forebrain (ACh) 5: septal nucleus (ACh) 6: amygdala

Brainstem, hypothal + sleep

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Physiological changes during sleep stages

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Control of feeding

1) *Appetite: Orexin* is produced by *lateral hypothalamus* + increases feeding 2) *Satiety: medial hypothal* - *Leptin* is produced by adipose tissue + feeds back to hypothal, which directs caloric disposal + reduced appetite - Blood glucose is monitored by many hypothalamic nuclei, important for energy homeostasis!

Homeostasis components

1) *Blood flow*: cardiac output, vasomotor tone, blood osmolarity, renal clearance, salt and water consumption 2) *Energy metabolism*: blood glucose level, appetite, digestion, metabolic rate, and temperature 3) *Reproduction*: gender identity, sexual orientation, fertility, mating behavior, pregnancy and lactation 4) *Stress response*: HPA axis, symp/ parasymp nervous systems, regional blood flow

Why do we need to sleep? (old, bad ideas)

1) *Conservation /replenishment of energy*: metabolic rate only 15% less during sleep, could be compensated by small amount of food - related idea: we sleep at night b/c it's colder, to save energy 2) *Behavioral immobilization theory*: Sleep keeps us safely immobilized during darkness - otherwise, we would bump into things /eaten by predators - sleep rhythms vary considerably between species! Predatory animals- long periods of sleep. Prey sleep shorter intervals (few min) - Dolphins solve problem of maintaining vigilance by having sleep alternate b/t the two cerebral hems

Other functions of RF

1) *Motor control*: connections enable RF to regulate muscle tone, postural mechs, orientation to external stimuli, voluntary movements of proximal body parts 2) *Respiration + circulation*: network of RF neurons in ventrolateral medulla is responsible for production of rhythmic breathing. Other RF neurons reg BP, distribution of blood vol, SV + HR 3) *Modulation of sensory info*: elimination of irrelevant sensory signals, so our attention can be focused on relevant signals - Summing up: RF activity essential for awareness of specific sensory stimuli and for adequate behavioral responses!

Hypothalamic afferents from limbic structures

1) *fornix* conveys info from hippocampus 2) *stria terminalis* travels near floor of lateral ventricle, nestled next to caudate, sending bidirectional info b/t hypothalamus + amygdala 3) Another, shorter pathway connecting amygdala + hypothalamus = *ventral amygdalofugal pathway* 4) *septal nuclei + nearby ventral striatum* 5) *orbitofrontal cortex* 6) other cortical areas

Control of thirst

1) *increased osmotic pressure* in supraoptic nucleus: --> Osmoreceptors trigger sensations of thirst, activating ADH release, water retention + drinking behavior 2) *Hypovolemia* also activates anterior hypothalamus through neural + hormonal mechs 3) *elevated body temp* also activates thirst

Posterior Region

1) *mammillary bodies* (limbic, b/t hippocampus + anterior thalamus) 2) *lateral nucleus* - *heat conservation*: promotes shivering + vasoconstriction - lesions here eliminate all temp regulation (*poikilothermia*) b/c also contains fibers from anterior region (which controls heat dissipation)

Hypothalamic nuclei: ventral

1) *tuber cinereum (TC) = floor*: swelling @ base of infundibulum (INF) 2) *median eminence* (ME), central floor to which infundibulum attaches 3) infundibulum: suspends pituitary /hypophysis