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 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?

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

5. 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

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 reduce Jet lag

11. later
sunset
earlier
sunrise
Lowest point in body temperature is usually 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. 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

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

20. 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)

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 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

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. 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

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