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The Journal of Neuroscience, April 15, 2003, 23(8):3555
Circadian and Homeostatic Regulation of Hypocretin in a
Primate Model: Implications for the Consolidation of Wakefulness
Jamie M.
Zeitzer,
Christine L.
Buckmaster,
Karen J.
Parker,
Craig M.
Hauck,
David M.
Lyons, and
Emmanuel
Mignot
Department of Psychiatry and Behavioral Sciences, Stanford
University, Palo Alto, California 94304
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.
Key words:
hypocretin; orexin; wake; sleep deprivation; squirrel monkey; homeostasis; circadian; cortisol; Saimiri; primate
Copyright © 2003 Society for Neuroscience 0270-6474/03/2383555-06$05.00/0
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