Hypocretin/Orexin Tonus and Vigilance Control

The importance of the hypocretin/orexin system in vigilance control has rapidly emerged from the discovery of narcolepsy genes in canines and mice and from the findings of ligand deficiency in human narcolepsy (1, 2, 3, 4). (An earlier anatomical study suggested this involvement [5].) Narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, and dissociated manifestations of REM sleep (6), is now known to be caused by the loss of hypocretin neurotransmission. The loss could be caused either by a malfunction in hypocretin ligand production or by a loss of function of one of the two hypocretin receptors (i.e., hypocretin receptor 2/orexin 2 receptor) (1).