The sleep-wake cycle, the hypocretin/orexin system and narcolepsy: advances from preclinical research to treatment

Abstract

Since their discovery in 1998, it has been shown that the orexin (hypocretin) peptides are involved in almost all of the functions historically associated with the lateral hypothalamus. These peptides are produced by only some thousand neurons restricted to the posterolateral hypothalamus. A decade later, the orexin neurons have emerged as an important mode of signalling in the hypothalamus. Orexins were recognized as regulators of feeding behaviour. The subsequent finding that an orexin deficiency causes narcolepsy in humans and animals indicates that these hypothalamic neuropeptides also have a crucial role in regulating sleep and wakefulness. Recent studies of orexin-producing neurons and their efferent and afferent systems, as well as phenotypic characterizations of mice with genetic alterations in the orexin system, have suggested further roles for orexin in the coordination of emotion, energy homeostasis, reward, drug addiction and arousal. In this special issue, we will discuss the role of orexins in sleep-wake regulation and its involvement in narcolepsy.