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1. Mechanisms of sleep and REM: a quartet model
2. Sleepless in Vienna: Von Economo Encephalitis Lethargica[1] Observed lesions in rostral midbrain and posterior hypothalamus resulted in narcolepsy.
Lesions in preoptic area and basal forebrain caused bouts of insomnia.
Predicted sleep-promoting neurons in hypothalamus near optic chiasm & wake promoting neurons in posterior hypothalamus.
3. The meaning of awake Main origin of W-R thalamic projection from caudal midbrain/rostral pons: cholinergic PPT/LDT.
Aminergic W-A groups project directly to the cortex.
VLPO possibly inhibited by TMN[3]
4. To sleep VLPO and ex-VLPO 80% GABA/Galanergic neurons densely innervating TMN, and slightly innervating LC
Ex-VLPO governs sleep, VLPO controls the mechanims of REM/NREM sleep.[4]
Inputs to these nuclei are poorly understood, however the destruction of Fos immunoreactive neurons correlated closely with loss of REM sleep.
5. The Sleep Switch
6. 2 process models use circadian drive and homeostat to explain bistable transitions between states.
H-H formalism performs this task via supercritical Hopf bifurcation.
26. Sleepless in Texas:Siffres famous experiment Overcome with lethargy and bitterness, I sit on a rock and stare at my campsite in the bowels of Midnight Cave, near Del Rio, Texas. Behind me lie a hundred days of solitude; ahead loom two and a half more lonely months. But I a wildly displaced Frenchman know none of this, for I am living beyond time, divorced from calendars and clocks, and from sun and moon, to help determine, among other things, the natural rhythms of life.
-Siffre, 1975
27. Siffres sacrifice: Subjects isolated from zeitgebers
Identified 2 rhythmic cycles in humans:
Right pictures a standard sleep cycle (which follows a period of 24.11 h.)
28. Dual oscillators Kronauer modeled the sleep cycle as 2 Van Der Pol oscillators (X n Y).
Increasing Y gave rise to phase trapping and other phenomena of sleepless subjects
But Y had no physical meaning.[5]
kronauer.ode
29. Ultradian Rhthyms Tamakawa et al. constructed more thorough neuromodulatory system
Ultradian homeostat (SS2) governs REM sleep[6]
During wake and REM, SS2 accumulates excitatory input to the x-VLPO, rates faster than homeostat (SS1)
31. Results:
32. Quartet classification of nuclei WA wake active
W-R wake/REM
N-R nonREM/REM
REM REM active
33. Triple Meep Model NREM/REM sleep and wake determined by activity of three theoretical cell groups.
Simplified Tamakawa
Contains information about qualitative cell states
triplecell.ode
34. Sleepy Meep Model Sleep deprivation hypothesis:
Cause extraneous input to amin groups (i.e. LC) via cortical projection.
Result decorrelation of fos protein causes intensification of sleep homeostat (SS1).
Further research: effect on SS2 unknown.
A second look at m.ode
35. 1. von Economo, C. (1930) Sleep as a problem of localization. J. Nerv. Ment. Dis. 71 249-259
2. Saper, Chou, Scammel (2001) The Sleep Switch: Hypothalamci Control of Sleep and Wakefulness. TRENDS in Neurosci. 24 726-731
3. Airaksinen, M.S. et al. (1992) Multiple Neurotransmitters in the Tuberomammillary Nucleus: Comparison of Rat, Mouse, and Guinea Pig. J. Comp Neurol. 323, 103-116
4. Steininger, T.L. et al. (2001) Subregional organization of preoptic area/anterior hypothalamic projections to arousal related monoaminergic cell groups. J Comp. Neurol. 429, 638-653
5. Strogatz, Steven (1986) The Mathematical Structure of the Human Sleep-Wake Cycle. Springer-Verlang
6. Tamakawa, et al. (2006) A Quartet Neural Model Orchestrating Sleep and Wakefulness Mechanisms. J. Neurophy 95 :2055-2069
Cover art by Shin, Yurin A. 2006
Thanks to Dennis Pearl, Avner Friedman, Janet Best, and David Terman