Brain Circuits Underlying Narcolepsy

Narcolepsy is a sleep disorder manifesting symptoms such as excessive daytime sleepiness and often cataplexy, a sudden and involuntary loss of muscle activity during wakefulness. The underlying neuropathological basis of narcolepsy is the loss of orexin neurons from the lateral hypothalamus. To date numerous animal models of narcolepsy have been produced in the laboratory, being invaluable tools for delineating the brain circuits of narcolepsy. This review will examine the evidence regarding the function of the orexin system, and how loss of this wake-promoting system manifests in excessive daytime sleepiness. This review will also outline the brain circuits controlling cataplexy, focusing on the contribution of orexin signaling loss in narcolepsy. Although our understanding of the brain circuits of narcolepsy has made great progress in recent years, much remains to be understood.