Biological Rhythms & Sleep Is there a biological clock? Is there a role for environmental cues? Neural substrates of the clock SCN Pineal gland Sleep

Environment Behavior Season Month 24 hs cycle (light/dark) Migration / Hibernation Menstrual cycle Wake / sleep Hormone release Body temperature Intra ocular pressure sensitivity to drugs Circa annual Circa dian Ultradian Hormone release; Most obvious ones: melatonin, cortisol Body temperature: if you go to sleep late, Yes: there is a correlation between the two eventually the cycle gets reset there are social cues No: jet lag babies wake up at 6 am if put to sleep at 7, 8, or 9 pm individual differences (early birds vs. owls) developmental differences (babies, adolescents, elderly) destroying SCN deletes cycle if I transfer certain cells of the hypothalamus from a subject who is early bird to one that is a late wake up subject, the Question: Does the environment drive the behavioral cycles?

How can we test this hypothesis? Assess the behavioral cycle when the environmental cue is absent (constant darkness) the environmental cue is shifted (jet lag) the environmental cue is not processed (retinal blindness)

Does the environment drive the behavioral cycles? Environmental cues Behavior Dark Activity Rest Light X Dark room situation Internal Clock

X 1. the cycle is driven by an internal clock Dark Activity Rest Light X Dark room situation Internal Clock (but with 25 hs cycle) 1. the cycle is driven by an internal clock 2. but environmental cues do entrain the clock

1. the cycle is driven by an internal clock 2. environmental cues do entrain the clock

Where in the brain is this Circadian Biological Clock? Light-dark cycle Constant dim light Lesion to the Suprachiasmatic nucleus (SCN) Gene mutation for Clock protein in SCN cells

Environmental cues reset the biological clock Bright Light can reduce Jet lag

later sunset earlier sunrise Lowest point in body temperature is usually 1-2 hs before wake-up Bright Light earlier than that point delays the cycle (‘later sunset’) Bright Light later than that point advances the cycle (‘earlier sunrise’)

SCN Biological Clock SCN cells have a circadian rhythm SCN lesions disrupt circadian rhythms SCN receives input from retina (light resets clock) SCN transplant: rhythm is controlled by donor’s cells The SCN clock has a genetic component (Clock/Per genes) Individual differences in sleep patterns may be related to these genetic differences (are you a ‘nigh owl’?) The circadian rhythm also depends on the pineal gland

The SCN clock has a genetic component The molecular changes oscillate with a 25 hs period - Light modulates the period

Pineal gland: Another part of the clock The pineal gland secretes melatonin Melatonin acts on SCN SCN acts on pineal gland, via the cervical ganglion of the sympathetic system Both SCN and pineal gland have circadian patterns

Melatonin release peaks soon after dark Melatonin is effective in reducing jet lag, BUT Its effectiveness depends on time of day because receptors for melatonin have circadian rhythm

Sleep Sleep Stages Sleep deprivation Sleep Functions Sleep pathology Behavioral profiles Neural Systems Developmental changes Sleep deprivation Sleep Functions Sleep pathology

Stages of Sleep REM Non-REM Desynchronized PGO waves Vivid dreams Stages 1 and 2 (light) Stages 3 and 4: slow-wave (synchronized) difficult to raise from it Muscle control (toss and turn) REM Desynchronized PGO waves Vivid dreams sexual arousal no muscle tone (paralysis)

REM: 1. Famous rock band; 2. Rapid-eye movements Behavior: Muscular Paralysis Penile Erection (not necessarily related to sexual dream) Cognition & Perception Dreams (w/ story line & perceptually rich) Neuronal Activity Desynchronize (EEG) PGO waves Cortical activation Neurotransmitters: High Ach Low NE (see Graph next slide) Low 5HT

Dreams REM Cerebral Cortex Lateral Geniculate Superior Nucleus colliculus Ach neurons PONS Neural Basis of Sleep Basal Forebrain – Ach (attention-arousal), GABA (SWS) Reticular Activating System (midbrain) – Arousal – Glu & Ach Locus Coeruleus (pons) – NE -> waking, inhibits REM sleep. Raphe Nucleus – 5-HT (serotonin) -> SWS sleep – inhibits reticular formation Pons (Ach) –->REM sleep – 1) caudal region - inhibition of muscle tone. 2) rostral region -> PGO waves Adenosine – build up during activity -> inhibits basal forebrain Ach systems. Caffeine is an adenosine antagonist. (-) Paralysis Nucleus In Brainstem Locus Coeruleus (Noradrenaline) Motoneurons

Developmental Changes in Sleep

Developmental Changes in Sleep Rhythm of Awake/Sleep Cycle: absent in newborns Overall Duration of Sleep: High in newborns, Reduced in the elderly Phases of Sleep Infants: Lots of REM, stage 4 Elderly: reduced REM Wake-up time Infants (< 2 years): Early (6-8 am), independent from bedtime!! Adolescent: late morning Elderly: Early morning Individual differences exist

young Elderly: Shorter cycles Reduced REM Reduced Stage 4

Sleep deprivation Increases irritability reduces cognitive performance May depress the immune system Extreme deprivation may produce death genetic mutation and/or thalamic lesion Rats under sleep deprivation (stress??) Reduced body temperature Immune suppression Increased metabolism

What is the Function of Sleep? Nobody knows! Sleep as an adaptive response? Found in all vertebrates (REM in mammals) Kept our ancestors our of predators way? Conserves energy (may be in small animals) Restoration and repair? Reduced brain activity during Slow Wave Sleep (Sws) Changes in sleep during: Prolonged bed rest (no real changes in SWS) Exercise (temperature increas. => increase SWS) Mental activity increases SWS (?) 9.12

What is the Function of Sleep? Memory consolidation Loss of sleep -> memory deficits Increased sleep after learning (?) Spatial learning in rats -> REM & place code cells

Sleep Disorders Sleep deprivation (social vs. biological factors) Toddlers: 9 pm bedtime vs. 6 am wake up Parents of infants: 11 pm bedtime vs. 6 am wake up Young adults: 8 am class vs. delayed wake up Insomnia: Difficulty in sleeping Many causes: situational, drug-induced Sleeping pills: drug-dependence insomnia

Sleep Disorders (cont’d) Narcolepsy: urge to sleep Triggered by boring events Genetic component (mice, dogs) Atrophy of hypocretin neurons in hypothalamus Quick transition from awake to REM Cataplexy: awake paralysis Triggered by exciting events Co-occurs with narcolepsy In normal subjects --> sleep paralysis

Sleep Disorders (cont’d) REM without atonia: ‘act out’ the dreams Disorder of slow wave sleep Sleep walking Night Terrors

Rhythms Is there a biological clock? Is there a role for environmental cues? Neural substrates of the clock SCN Pineal gland

Sleep deprivation Increases irritability reduces cognitive performance May depress the immune system Extreme deprivation may produce death genetic mutation and/or thalamic lesion Rats under sleep deprivation (stress??) Reduced body temperature Immune suppression Increased metabolism

Activities sleep diary (ask george) morning/evening questionnaire