The Orexin System. Basic Science and Role in Sleep Pathology

Orexins (hypocretins) and their receptors were discovered in 1998. Orexin neuropeptides are produced by a very small number of cells in the lateral hypothalamus, suggesting a fundamental role in homeostasis. Despite the name “orexin,” which was coined after the original discovery of its role in appetite regulation, the orexin system has foremost emerged as a crucial player in the maintenance of wakefulness and vigilance. The orexin system is highly conserved across vertebrates; its role in arousal and wakefulness stabilization is essential and cannot be replaced by another brain circuit. The discovery of hypocretin/orexin rapidly led to the hypothesis of its pathogenic contribution in the abnormal state of hyperarousal of insomnia and, for its deficiency, in narcolepsy and cataplexy.