Neurobiological Correlates of Sleep Homeostasis
Final rept. 15 Sep 1995-31 Dec 1998
STANFORD UNIV CA SPONSORED PROJECTS OFFICE
Pagination or Media Count:
This research was intended to examine molecular aspects of sleep homeostasis in the brain. Our experiments were guided by the two-process model of sleep regulation which posits that an increased homeostatic drive to sleep occurs during prolonged wakefulness. We found that expression of brain-derived neurotrophic factor BDNF mRNA increases in the rat cortex during a 6 hr sleep deprivation period. Increased BDNF mRNA levels likely results in elevated expression of BDNF protein which we hypothesize may protect neurons from the potentially deleterious effects of prolonged sensory stimulation during wakefulness. In the course of these studies, we cloned a novel gene, hypocretin, that encodes two biologically active neuropeptides expressed within a very restricted area of the posterior hypothalamus. When injected into the lateral ventricles of the brain, the hypocretin peptides stimulate food intake, increase wakefulness and decrease deep slow wave sleep and REM sleep. In humans, the sleep disorder narcolepsy has recently been associated with degeneration of the hypocretin neurons. We have therefore proposed a model in which the hypocretins play a central role in arousal state i.e., sleepwake regulation. We also studied gene expression in the hibernating brain, as another model of arousal state.
- Anatomy and Physiology
- Stress Physiology