Research in the Scammell Lab focuses on the neurobiology of sleep and the neural basis of narcolepsy. Narcolepsy is caused by an extensive and selective loss of the hypothalamic neurons that produce the orexin neuropeptides (also known as hypocretins). This cell loss generally occurs in the teens or young adulthood and results in lifelong sleepiness and cataplexy, brief episodes of muscle weakness that are similar to the paralysis that occurs during REM sleep. Much of our current work focuses on mouse models of narcolepsy because mice lacking orexins also have sleepiness and frequent episodes of cataplexy. We hypothesize that orexins normally stabilize the activity of wake-promoting brain regions, but absence of orexins produces behavioral state instability, with rapid transitions from wakefulness into sleep, and intrusions into wakefulness of REM sleep elements such as cataplexy or hallucinations.
Figure: The orexin neurons innervate many brain regions that promote wakefulness and suppress REM sleep, including the basal forebrain and monoaminergic nuclei.
