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Mechanisms of sleep and REM: a quartet model

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Mechanisms of sleep and REM: a quartet model

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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: Siffre’s 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. Siffre’s 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

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