Hypocretin

Orexin signaling is provided by diffusely distributed fibers and involved in different brain circuits that orchestrate sleep and wakefulness states. Here, the authors show that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus and exhibit rapid eye movement (REM) sleep-related actions.

Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.

Narcolepsy is a sleep disorder caused by selective loss of orexin-producing neurons. Scammell and colleagues describe the functions of orexin neurons and the effects of their loss and review evidence implicating the immune system in the pathogenesis of the disorder.