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The hypocretins (also called the orexins) are two neuropeptides derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein coupled receptors for the hypocretins have been identified, and these show different distributions within the central nervous system and differential affinities for the two hypocretins. | ềFEBS Journal MINIREVIEW The hypocretins and sleep Luis de Lecea and J. Gregor Sutcliffe Department of Molecular Biology The Scripps Research Institute La Jolla CA USA Keywords arousal lateral hypothalamus narcolepsy orexin wakefulness Correspondence L de Lecea Department of Molecular Biology The Scripps Research Institute 10550 N. Torrey Pines Road La Jolla CA 92037 USA Fax 1 858 784 9120 Tel 1 858 784 2816 E-mail llecea@scripps.edu Received 21 June 2005 accepted 20 September 2005 doi 10.1111 j.1742-4658.2005.04981.x The hypocretins also called the orexins are two neuropeptides derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein coupled receptors for the hypocretins have been identified and these show different distributions within the central nervous system and differential affinities for the two hypocretins. Hypocretin fibers project throughout the brain including several areas implicated in regulation of the sleep wakefulness cycle. Central administration of synthetic hypocretin-1 affects blood pressure hormone secretion and locomotor activity and increases wakefulness while suppressing rapid eye movement sleep. Most human patients with narcolepsy have greatly reduced levels of hypocretin peptides in their cerebral spinal fluid and no or barely detectable hypocretin-containing neurons in their hypothalamus. Multiple lines of evidence suggest that the hypocretinergic system integrates homeostatic metabolic and limbic information and provides a coherent output that results in stability of the states of vigilance. Discovery of the hypocretins Observations on humans and experimental animals with localized hypothalamic lesions led to the earliest notions about the role of the lateral hypothalamus LH . From studying patients with encephalitis letharg-ica von Economo 1 proposed that the posterior hypothalamus including the LH was required for maintaining the awake state. The signaling .
