SLEEP & CIRCADIAN RHYTHMS

1. SLEEP & CIRCADIAN RHYTHMS Images in these slides were obtained from the following sources: Carlson, Physiology of Behavior, 9th edition (2007) Allyn and Bacon Rosenzweig, Leiman and Breedlove, Biological Psychology (2001) Sinaur Associates, Inc

2. SLEEP PHYSIOLOGY • PHYSIOLOGICAL MEASURES • Electroencephalogram (EEG) • brain waves from scalp surface • Electrooculogram (EOG) • eye movements • Electromyogram (EMG) • muscle tone

3. SLEEP PHYSIOLOGY • EEG Waves (wakefulness) • beta waves • Irregular low amp., high freq. waves (13-30 Hz) • indicative of alert and vigilant activity • alpha waves • regular medium freq. waves (8-12 Hz) • resting quietly, but awake

4. SLEEP PHYSIOLOGY • SLEEP STAGES • Stage 1: alpha and theta waves (initial) • Stage 2: K complexes, sleep spindles • Stage 3: 20-50% delta (SWS) • Stage 4: > 50% delta (SWS) • REM (emergent stage 1)

5. SLEEP PHYSIOLOGY • REM SLEEP • increased cerebral activity, erratic EEG (beta and theta waves) • rapid eye movements • loss of core muscle tone (paralysis) • autonomic arousal (elevated hr, bp, and respiration) • narrative dreams with much visual imagery • initially referred to as “PARADOXICAL SLEEP”

6. SWS VS. REM SLEEP

7. SLEEP CYCLES

8. SLEEP PATTERNS • Percent of SWS vs. REM changes with age • Young Adult sleep patterns consist of: • 7-8 hours of 90-110 min. repeating cycles • 45-50% of total sleep is stage 2 • 20% of total sleep is REM sleep • More SWS early in night • Progressive lengthening of REM periods

9. LIFE SPAN CHANGES IN SLEEP • Daily sleep rhythms begin ~ 16 weeks. • Greater % REM in infants and children. • REM component decreases with age. • Total sleep time decreases with age. • Elderly frequently experience insomnia and decreased SWS.

10. LIFE SPAN CHANGES IN SLEEP

11. SLEEP DISORDERS • INSOMNIA • affects ~25% of population occasionally, ~9% regularly • No single definition • Insomnia is symptom, not a disease • multiple causes, often iatrogenic • tolerance to sedative-hypnotic drugs • frequent symptom of depression • Other causes: sleep apnea, nocturnal myoclonus, restless legs (PLMD)

12. SLEEP DISORDERS • Sleep-onset insomnia • difficulties falling asleep • Sleep maintenance insomnia • frequent awakenings, may be associated with SLEEP APNEA (difficulty breathing while asleep)

13. SLEEP DISORDERS • NARCOLEPSY • Characteristic Symptoms: • Sleep Attack (5-30 minutes) • Cataplexy • frequently brought on by intense emotions • Immediate REM at sleep onset • Sleep Paralysis • Hypnogogic Hallucinations

14. SLEEP DISORDERS • NARCOLEPSY • Heritability and Hypocretin (Orexin) • Genetic models in dogs • increased ACh receptors in pons • amygdala and forebrain degeneration • canarc gene (Hypocretin 2 receptors) • Hypocretin gene knockout mouse model • CSF analysis in human narcoleptic patients show diminished hypocretin levels.

15. SLEEP DISORDERS • REM SLEEP BEHAVIOR DISORDER • Characterized by failure to exhibit muscle paralysis during REM sleep • Appears to be neurodegenerative disorder with some possible genetic component • Often associated with other neurodegenerative disorders, such as Parkinson’s disease • Usually treated with clonazepam, a benzodiazepine

16. SLEEP DISORDERS • COMMON CHILDHOOD SLEEP DISORDERS ASSOSCIATED WITH SLOW WAVE SLEEP • PavorNocturnus (night terrors) • Somnambulism (sleep walking) • Nocturnal Enuresis (bed wetting)

17. SLEEP FUNCTIONS(Why do we sleep?) • Restorative Functions • growth and repair • Adaptive Functions • predator avoidance • energy conservation • Cognitive Functions • learning, unlearning, reorganization

18. COMPARATIVE STUDIES OF SLEEP

19. SLEEP IN MARINE MAMMALS

20. SLEEP DEPRIVATION • Early reports of bizarre or psychotic behavior • Wide individual variability (personality and age factors) • Most common effects of sleep deprivation: • increased irritability • decreased concentration • Confusion/disorientation

21. SLEEP DEPRIVATION IN HUMANS • Performance on brief tasks is unimpaired. • Performance on tasks that involve high motivation are generally not impaired. • Sleep Recovery (Randy Gardner story) • 11 days (264 hours) sleep deprivation • 1st night, ~ 15 hours; stage 4 increased at expense of stage 2 • 2nd night, ~10 hours; greatest REM recovery • Percentages of sleep recovery not equivalent across all stages: 7% of stages 1 and 2, 68% SWS, 53% REM sleep “made up”

22. SLEEP DEPRIVATION IN NONHUMANS • It is difficult to tease apart effects of sleep deprivation versus stressful effects of the procedure. • Rechtschaffen and Bergmann, 1995 • Carousel apparatus with yoked controls • Experimental animals died within days, while controls remained relatively healthy.

23. EFFECTS OF ACTIVITIES ON SLEEP • Effects of Exercise on Sleep • Does the brain recover from day time physical exertion? • Little compelling evidence: People who spend much of their time resting in bed do not sleep less • Effects of Mental Activity on Sleep • Does the brain recover from day time mental exertion? • Some studies have shown that extensive mental activities are followed by normal sleep duration, but increased SWS.

24. FUNCTIONS OF REM SLEEP • Theories that REM sleep is required for normal • Mental health • Motivation • Cognitive processing • Interesting links between REM sleep and depression • REM deprivation has antidepressant effects • Most antidepressant drugs also reduce REM sleep. • There’s considerable research on links between REM sleep and learning/memory.

25. REM SLEEP DEPRIVATION • Following REM deprivation, there is a compensatory increase in REM sleep, which seems to suggest REM sleep is a necessary brain function. • Some evidence that REM deprivation can produce cognitive/memory deficits. • Some evidence that REM sleep increases following new learning.

26. NEURAL MECHANISMS OF SLEEP • Basal Forebrain • Brain Stem Reticular Formation • Raphe nucleus (midbrain) • Locus Coeruleus (pons) • Lateral hypothalamus

27. NEURAL MECHANISMS OF SLEEP • Sleep is an active state mediated by at least three neural systems • Forebrain: generates SWS • Reticular Formation: Wakes Forebrain • Pons: Triggers REM sleep

28. NEURAL MECHANISMS OF SLEEP • Bremer (1935) • Encephale isole • Cerveau isole • Moruzzi and Magoun (1949) • Reticular formation • Jouvet (1967) • Raphe system

29. NEURAL MECHANISMS OF SLEEP • BASAL FOREBRAIN • ventral frontal lobe, anterior hypothalamus • lesions abolish SWS • electrical or heat stimulation can induce SWS activity • These neurons are active at sleep onset • Inhibited by NE stimulation

30. NEURAL MECHANISMS OF SLEEP • RETICULAR FORMATION • central core of brain stem • diffuse group of cells extending from medulla to thalamus • electrical stimulation produces arousal, awakens a sleeping animal • lesions produce persistent sleep

31. NEURAL MECHANISMS OF SLEEP • RAPHE NUCLEI • A system of serotonergic neurons along midline of brain stem. • Lesions to Raphe nuclei produce insomnia. • PCPA inhibits 5-HT synthesis and reduces sleep, whereas 5-HT agonists promote sleep

32. NEURAL MECHANISMS OF SLEEP • PONS • crucial for REM sleep components • lesions ventral to Locus Coeruleus abolish REM sleep • electrical or pharmacological stimulation (ACh agonists) can induce or prolong REM sleep • small lesions ventral to LC selectively abolish REM muscle atonia

33. NEUROTRANSMITTERS AND SLEEP

34. CIRCADIAN RHYTHMS • DEFINITION • 24 hr. endogenous cycles • EXAMPLES • sleep/wake cycle • body temperature • hormone secretion • drug sensitivity

35. LABORATORY STUDIES OF CIRCADIAN RHYTHMS

36. CIRCADIAN RHYTHMS • TERMINOLOGY • Free Running Period • Entrainment • Zeitgeber • Phase Shifts • phase advances: acceleration of circadian rhythm • phase delays: deceleration of circadian rhythm

37. CIRCADIAN RHYTHMS • Circadian Timing Mechanisms • Internal desynchronization of S-W cycle and body temp. cycle suggest separate timing mechanisms. • Common Examples of Phase Shifts • Jet Lag results from phase shifts in circadian rhythms as a result of traveling across time zones. • Shift workers often forced to adjust S-W cycle. Such disruptions may affect health and productivity.

38. NEURAL MECHANISMSOF CIRCADIAN RHYTHMS

39. SUPRACHIASMATIC NUCLEUS • Experimental Research on SCN involvement in circadian rhythms • Large lesions of hypothalamus disrupt circadian cycles of activity in rats. (Richter, 1967) • Lesions specific to SCN disrupt periodicity of sleep/wake cycle • SCN displays circadian cycles of electrical, metabolic, and biochemical activity. • Fetal tissue transplants in hamsters • Fetal tissue from 20 hour donor implanted in 25 hour recipient after SCN lesion. • Recipient becomes entrained to 20 hour cycle

40. SUPRACHIASMATIC NUCLEUS