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The Journal of Neuroscience, March 1, 2001, 21(5):1656-1662
Fos Expression in Orexin Neurons Varies with Behavioral State
Ivy V. Estabrooke1, Marie T. McCarthy1, Emily Ko2, Thomas C. Chou3, Richard M. Chemelli4, Masashi Yanagisawa4, Clifford B. Saper1, 3, and Thomas E. Scammell1 1 Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, 2 Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, 3 Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, and 4 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235
The neuropeptide orexin (also known as hypocretin) is hypothesized to play a critical role in the regulation of sleep-wake behavior. Lack of orexin produces narcolepsy, which is characterized by poor maintenance of wakefulness and intrusions of rapid eye movement (REM) sleep or REM sleep-like phenomena into wakefulness. Orexin neurons heavily innervate many aminergic nuclei that promote wakefulness and inhibit REM sleep. We hypothesized that orexin neurons should be relatively active during wakefulness and inactive during sleep. To determine the pattern of activity of orexin neurons, we recorded sleep-wake behavior, body temperature, and locomotor activity under various conditions and used double-label immunohistochemistry to measure the expression of Fos in orexin neurons of the perifornical region. In rats maintained on a 12 hr light/dark cycle, more orexin neurons had Fos immunoreactive nuclei during the night period; in animals housed in constant darkness, this activation still occurred during the subjective night. Sleep deprivation or treatment with methamphetamine also increased Fos expression in orexin neurons. In each of these experiments, Fos expression in orexin neurons correlated positively with the amount of wakefulness and correlated negatively with the amounts of non-REM and REM sleep during the preceding 2 hr. In combination with previous work, these results suggest that activation of orexin neurons may contribute to the promotion or maintenance of wakefulness. Conversely, relative inactivity of orexin neurons may allow the expression of sleep.
Key words: orexin; hypocretin; Fos; wake; wakefulness; sleep; REM; lateral hypothalamus; perifornical region; hypothalamus; thermoregulation; rat
Copyright © 2001 Society for Neuroscience 0270-6474/01/2151656-07$05.00/0
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