Fos expression in orexin neurons varies with behavioral state

The neuropeptide orexin (also known as hypocretin) is hypothesized to play a critical role in the regulation of sleep-wake behavior. Lack of orexin pr oduces narcolepsy, which is characterized by poor maintenance of wakefulnes s and intrusions of rapid eye movement (REM) sleep or REM sleep-like phenom ena into wakefulness. Orexin neurons heavily innervate many aminergic nucle i that promote wakefulness and inhibit REM sleep. We hypothesized that orex in neurons should be relatively active during wakefulness and inactive duri ng sleep. To determine the pattern of activity of orexin neurons, we record ed sleep-wake behavior, body temperature, and locomotor activity under vari ous conditions and used double-label immunohistochemistry to measure the ex pression of Fos in orexin neurons of the perifornical region. In rats maint ained on a 12 hr light/ dark cycle, more orexin neurons had Fos immunoreact ive nuclei during the night period; in animals housed in constant darkness, this activation still occurred during the subjective night. Sleep deprivat ion or treatment with methamphetamine also increased Fos expression in orex in neurons. In each of these experiments, Fos expression in orexin neurons correlated positively with the amount of wakefulness and correlated negativ ely 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 o rexin neurons may contribute to the promotion or maintenance of wakefulness . Conversely, relative inactivity of orexin neurons may allow the expressio n of sleep.