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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)
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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.
- Fall '11