Hypocretin articles from across Nature Portfolio

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.