Biological Rhythms & Sleep

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

2. Environment Season Month 24 hs cycle (light/dark) Behavior Migration / Hibernation Menstrual cycle Wake / sleep Hormone release Body temperature Intra ocular pressure sensitivity to drugs Circa annual Circa dian Ultradian Question: Does the environment drive the behavioral cycles?

3. 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)

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

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

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

8. 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

10. Environmental cues reset the biological clock Bright Light can reduceJet lag

11. 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’)

12. 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

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

14. 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 Pineal gland: Another part of the clock

15. 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

17. Sleep • Sleep Stages • Behavioral profiles • Neural Systems • Developmental changes • Sleep deprivation • Sleep Functions • Sleep pathology

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

21. 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

23. Dreams REM Cerebral Cortex Superior colliculus Lateral Geniculate Nucleus Ach neurons PONS (-) Paralysis Nucleus In Brainstem Locus Coeruleus (Noradrenaline) Motoneurons

25. Developmental Changes in Sleep

26. 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

27. young • Elderly: Shorter cycles Reduced REM Reduced Stage 4

28. 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

30. 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

31. 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

32. Sleep Disorders • Sleep deprivation (social vs. biologicalfactors) • 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

33. 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

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

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

36. 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

37. Activities • sleep diary (ask george) • morning/evening questionnaire