29 Circadian Rhythms

29 Circadian Rhythms - PSL302: Lecture 29, by Prof. MacKay!...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: PSL302: Lecture 29, by Prof. MacKay! Wednesday, Nov. 24, 2010 Circadian Rhythms - Governed by neuronal oscillator w/ near-24h period (in suprachiasmatic n.) - Entrained to exact day-night cycle by retinal input from ganglion cells w/ melanopsin - Absorb light: ganglion cells discharge -> depolarizing - Cone + rod ganglions -> hyperpolarizing - Retinal directly project to 1) Suprachiasmatic nucleus (SCN), or to 2) Pretectal nucleus: sympathetic efferents -> sup.cervical ganglion -> pineal body Circadian Rhythms & Learning - Govern pupillary light reflex: projections down to thoracic cord -> sympathetic efferents up to sup. cervical ganglion -> dim light = open pupil - One of the targets: pineal body - Darkness turns off pineal body via sympathetic system Circadian Modulation - Hormone synthesis and secretion - Glucocorticoid steroids (waking up) - Body temperature (min=late night, max=day) - Autonomic behaviours (e.g. feeding) - Mood - Alertness - Sleep-wake cycle Diagram: locating the suprachiasmatic n. - At bottom of hypothalamus (by pituitary) - In the wall of IIIrd ventricle - On top of optic chiasm (at midline) - Ganglion axons w/ melanopsin terminate here - Same position as arcuate n. (further back) 24-hr oscillator - Strictly speaking, not a neuronal oscillator: neuronal activity can't produce oscillations w/ such long periods -> work at "seconds" level - So requires long metabolic processes - Based on gene transcription + translation - Genes + protein product interactions => negative feedback loop (w/ gene transcription) - Mechanism located in suprachiasmatic n. of hypothalamus: "master circadian clock" - Also found in tissues throughout body, i.e. lungs, kidneys, etc. - Coordinated by suprachiasmatic n. -> what coordinates this? - Modulated by 1) Retinal input, i.e. melanopsin ganglion activity 2) Pineal input, e.g. seasonal variations: night phase longer in winter,shorter in summer 3) Reticular activating systems (serotonin): influence relative phases of oscillator Based on gene transcription and translation: - I.e. Stressed out: you can't sleep! Day phase lengthens, night phase contracts N 24 hr oscillator genes and protein product interactions form a negative feedback loop mechanism located in suprachiasmatic n. of hypothalamus: master circadian clock 1 of 5 modulated by 1) retinal input; 2) pineal input; e.g. seasonal variations; 3) reticular PSL302: Lecture 29, by Prof. MacKay! Wednesday, Nov. 24, 2010 Pineal body - Activated via sympathetic system in darkness (cf. Pupillary light reflex) - Secretes melatonin - Blocked by even small amts of light (esp blue-green) - Melanopsin: peak absorbance at blue-green spectrum (like rhodopsin) - Blind to true red light -> won't block melatonin secretion - Melatonin involved in sleep induction (necessary for sound sleep) - Maximal secretion at ~2am - Higher secretion in summer than winter Diagram: dorsal surface of brainstem Circadian Rhythms & Learning - At diencephalon: pineal body at midline, on top of superior colliculi - Secretes melatonin into CSF - -> encircling blood vessels - Pituitary body on ventral side - At midbrain: superior+inferior colliculi Sleep-wake Cycle - At Pons: cerebellum peduncles - IVth ventricle underneath `sleep switch' in ventrolateral preoptic n of sleep switch n. Sleep-wake cycle circadian clock, 2) sleep debt (brain - Controlled by two centers in hypothalamus: i.e. temperature control (closely); inhibitory glycogen , adenosine related) - Sleep switch in ventrolateral preoptic nucleus (VLPO) of anterior hypothalamus nucleus `waking switch' in tuberomamillary - Beside hypothalamus zone that cools down body histamine activating system: excitatory to - Activated by brainstem activating systems 1) Circadian clock (in suprachiasmatic 2 activity switch = sleep) n.: centers mutually inhibit each other 2) Sleep debt (brain glycogen , adenosine = sleep) - Inhibitory: to activating systems in brainstem + histaminergic system - Waking switch in tuberomamillary nucleus (TMN) of histamine activating system - Excitatory: to brainstem activating systems - 2 centers mutually inhibit each other Diagram: sagittal section of hypothalamus - Ant. hypothalamus (left): VLPO -> sleep - Above SCN + optic chiasm - Post. hypothalamus (right): TMN -> wake - Close to mamillary nuclei - Histaminergic neurons located here - Turns on activating systems -> Reciprocal inhibition: VLPO <-> TMB - Dorsal hypothalamus: orexinergic neurons anterior hypothalamus: activated by 1) November 24, 2010 2 of 5 4 Circadian Rhythms & Learning November 24, 2010 Stages of Sleep Wednesday, Nov. 24, 2010 PSL302: Lecture 29, by Prof. MacKay! Histamine Activating System REM dream episodes (same brain rhythms as waking state) Light sleep (stages 1 & 2) deep Orexin (hypocretin) sleep (stages 3 & 4, `slow wave') -Orexinergic neurons in dorsal hypothalamus period of cycle through these stages with a -Activated by SCN -> excite TMN about 90 min (ultra-dian rhythm) -Stabilizes + sustains waking state in relation to REM sleep important for learning/memory circadian cycle -Lesion results in narcolepsy -Also provide circadian drive for feeding (via paraventricular nucleus) Stages of Sleep Diagram: record potentials outside scalp - Must have synchronized activity of brain neurons -> synaptic potentials (EPSPs > IPSPs) Orexin alpha rhythms - Waking state: (hypocretin) (10 cycles/s) + beta rhythms (20 cycles/s) Orexinergic neurons in dorsal hypothalahypothala - REM dream episodes: "rapid eye mvt" as dream mus: activated by SCN; excite TMN - Same rhythms as waking state stabilizes waking state in relation to - Lightest stage of sleep circadian cycle repeatedly - Occurs lesion sleep (stages 1 py - Light results in narcolepsy & 2) also provide circadian drive for feeding (via - Stage 1: theta rhythms paraventricular nucleus) - Stage 2: spindles+K complex - Deep sleep (stages 3 & 4) - Stage 3-4: delta rhythms (1-2 cycles/s, huge amplitude = synchronization - Stage 4: slow wave - Cycle thru these stages w/ period of ~90min = ultra-dian rhythm 5 - REM sleep + slow wave sleep important for learning/memory - As you progress thru cycle, enter deeper and deeper sleep - But as you progress thru night, shorter slow wave sleep + more REM sleep -> approach waking state Circadian Rhythms & Learning November 24, 2010 - Ultra-dian rhythms don't stop when you wake up -> now cycling btwn stages of alertness - Around 2-4pm, siesta stage (low pt in alertness) Ultradian rhythms -Not controlled by master clock in SCN -Timed by a faster (~90min) oscillator that influences the brainstem reticular activating systems -SCN master clock is a 24h oscillator: governs hormonal lvls that determine time of falling asleep and waking 3 of 5 Ultradian Rhythms PSL302: Lecture 29, by Prof. MacKay! Wednesday, Nov. 24, 2010 Sleep atonia - Brain is awake but important that you don't act them out! - Large reticulospinal + corticospinal neurons very active in REM sleep - BUT no body mvt, just eye mvt = sleep atonia (muscles paralyzed) Circadian Rhythms & Learning - Spinal motoneurons hyperpolarized (up to 10mV) by inhibitory reticulospinal system (pons) - Not likely a specific inhibitory nucleus - Possible to wake up while still in REM paralysis -> sleep paralysis - Doesn't affect brainstem: eye mvts, breathing+mouth mvts intact Explicit memory Activating Systems of events and facts are consolidated--into other brain areas--by the hippocampal - Strongly modulated during sleep stages region; requires REM and slow wave sleep - Serotonergic/noradrenergic: maximal discharge in waking, silent in REM sleep e.g. memory of a visual hierarchy of zones: object - Sustains locomotion when awake and paralysis during dreaming in `perirhinal' cortex memory of a spatial environment in - Slows progressively stage 1--> stage 4 hippocampus proper - Cholinergic: midbrain center supports waking - Pontine center (in n. parabrachialis?) supports REM sleep - Slows progressively stage 1--> stage 4 BUT very active during REM sleep - Pontine inhibitory cells cause sleep atonia Explicit Memory - Explicit (episodic and semantic) memories of events + facts are consolidated (+ stored into other brain areas) by the hippocampal region (of limbic cortex) Circadian Rhythms & Learning - Consolidation requires REM + slow wave sleep - Dreaming episodes: repetitions of events of previous day -> put into memory - Slow wave sleep: very diff dreams from REM & you can never recall them - Hierarchy of zones: - Memory of a spatial envmt (whole scene: objects in relation to each other) in hippocampus proper - Memory of particular visual objects in perirhinal cortex Hippocampal place cells - Respond to spatial locations in envmt as you pass thru them Circadian Rhythms & Learning - Consolidate memory of specific locations - Probably not memory store - Necessary to move thru envmt for neuronal response - Highly integrated sensory, motor + motivatonal input Explicit (episodic and semantic) memories November 24, 2010 November 24, 2010 9 November 2 Hippocampal place cells Diagram: rat moving thru maze - Place cells discharging pattern in mice brains Respond to spatial locations in the - Learned how to get to food environment as you pass through them - At y location (around corner), place cell discharges maximally upon consolidate memory of that location recognizing area probably not memory store - Doesn't matter which direction he's facing necessary to move through environment for neuronal response; highly integrated - Learned how to go around corner to get food sensory, motor and motivational input 4 of 5 10 Long-term potentiation (LTP) PSL302: Lecture 29, by Prof. MacKay! Wednesday, Nov. 24, 2010 Long-term potentiation (LTP) - How do you lay down memories in brain? Long-term potentiation of synaptic cxns - Synaptic mech of memory formation - Occurs initially in hippocampus but also throughout NS (memories stored throughout) - Repeated high freqcy stimulation of a synapse = EPSP size - Can also work for inhibitory synapses - LTP in hippocampus can last for a week or 10 daysLearning Circadian Rhythms & - Useful for learning + cramming, characteristic of most memories - Incl. motor memories (implicit or habitual memory: when you're learning new motor skill - But don't need hippocampus or amygdala -> operates in sensory motor zones - If you want motor memories built in strongly, develop during childhood - Mediated by a special glutamate receptor (NMDA receptor, ionotropic) - Must be depolarized before it will open a channel for Ca++ diffusion - Glutamate binds -> open pore = allow Ca++ diffusion BUT pore blocked by Mg++ - Remove Mg++ by depolarizing membrane: - When membrane polarized, Mg++ attracted to -vely charged inner membrane - Requires other cation channels to open - Other ionotropic glutamate receptors must be present -> depolarize membrane - Must have high freqcy input into post-synaptic cell = lots of EPSP summation -> depolarization -> Ca++ influx -> LTP process LTP Mechanism - Influx of Ca++ has several fxns: - Phosphorylation of membrane proteins to enhance ionotropic EPSPs - Activate enzymes, which allow... - Generation of retrograde transmitters (e.g. endocannabinoids, NO) - Travel to presynaptic terminal to Circadian Rhythms & Learning vesicle release probability LTP mechanism - Trigger transcription/translation - More post-synaptic receptors, larger synaptic size - Key for maintaining LTP Influx of calcium ion activates enzymes Diagram: Retrograde transmitter action - Ca++ influx turn on NO synthase - NO diffuses everywhere (not containable) - Target: pre-synaptic terminal -> binds to guanylyl cyclase receptor -> [cGMP] - Facilitate exocytosis = transmitter released = LTP - Endocanniboids: inhibitory retrograde transmitter - LTP is plastic process -> in parallel, depression of synapses - LTD: remove receptors from post-synaptic membrane = silent synapse Nov November 2 phosphorylation of membrane proteins to enhance ionotropic EPSPs generation of retrograde transmitters ( g O); (e.g. NO); travel to p y p Ca terminal to presynaptic increase vesicle release probability trigger transcription/ translation: more postsynaptic receptors, larger synaptic size Retrograde Transmitter (long term potentiation) ++ 5 of 5 ...
View Full Document

This note was uploaded on 03/27/2012 for the course PSL PSL300 taught by Professor Mackayfrench during the Fall '11 term at University of Toronto.

Ask a homework question - tutors are online