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      Circadian and Homeostatic Regulation of Hypocretin in a Primate Model: Implications for the Consolidation of Wakefulness

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          Abstract

          In humans, consolidation of wakefulness into a single episode can be modeled as the interaction of two processes, a homeostatic “hour-glass” wake signal that declines throughout the daytime and a circadian wake-promoting signal that peaks in the evening. Hypocretins, novel hypothalamic neuropeptides that are dysfunctional in the sleep disorder narcolepsy, may be involved in the expression of the circadian wake-promoting signal. Hypocretins (orexins) are wake-promoting peptides, but their role in normal human sleep physiology has yet to be determined. We examined the daily temporal pattern of hypocretin-1 in the cisternal CSF of the squirrel monkey, a New World primate with a pattern of wake similar to that of humans. Hypocretin-1 levels peaked in the latter third of the day, consistent with the premise that hypocretin-1 is involved in wake regulation. When we lengthened the wake period by 4 hr, hypocretin-1 concentrations remained elevated, indicating a circadian-independent component to hypocretin-1 regulation. Changes in the stress hormone cortisol were not correlated with hypocretin-1 changes. Although hypocretin-1 is at least partially activated by a reactive homeostatic mechanism, it is likely also regulated by the circadian pacemaker. In the squirrel monkey, hypocretin-1 works in opposition to the accumulating sleep drive during the day to maintain a constant level of wake.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 April 2003
          : 23
          : 8
          : 3555-3560
          Affiliations
          [ 1 ]Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California 94304
          Article
          PMC6742340 PMC6742340 6742340 7545
          10.1523/JNEUROSCI.23-08-03555.2003
          6742340
          12716965
          4b219750-8b51-4663-a9f7-12a4e1b1f4b8
          Copyright © 2003 Society for Neuroscience
          History
          : 14 November 2002
          : 11 February 2003
          : 11 February 2003
          Categories
          ARTICLE
          Behavioral/Systems/Cognitive
          Custom metadata
          5.00

          primate,squirrel monkey,cortisol,homeostasis,wake, Saimiri ,circadian,hypocretin,sleep deprivation,orexin

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