Korean J Psychopharmacol.  2007 May;18(3):133-142.

Neuroanatomy of Sleep-Wake Regulation and its Application to Pharmacotherapy

  • 1Department of Psychiatry, Keimyung University School of Medicine, Daegu, Keimyung University Dongsan Medical Center, Sleep Clinic, Daegu, Korea. mdhck@dsmc.or.kr


A current hypothesis of sleep-wake regulation proposes that the sleep process starts with the activation of sleep-promoting neurons located in the preoptic area of the anterior hypothalamus. This activation leads to the inhibition of wake-promoting neurons located in the posterior hypothalamus, basal forebrain, and mesopontine tegmentum, which, in turn removes inhibition from the sleep-promoting structures(i.e., disinhibition) to initiate the sleep process. Mutual inhibition between these wake- and sleep-promoting neurons results in switching properties that define discrete wakeful and sleep states with sharp transitions between them. Wake-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei, and possibly the dopaminergic ventral tegmental area. The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. The regulation of sleep is classically viewed as the dual interaction of circadian(SCN-based) and homeostatic processes, and the propensity to be asleep or awake at any given time is a consequence of a sleep debt and its interaction with signals from the SCN circadian clock. To better understand the mechanisms of sleep and wakefulness, the focus of pharmacotherapy is on targeting specific therapies to the particular defect in sleep-wake regulation.


Neuroanatomy; Circadian rhythm; Sleep disorders; Hypothalamus

MeSH Terms

Circadian Clocks
Circadian Rhythm
Drug Therapy*
Hypothalamic Area, Lateral
Hypothalamus, Anterior
Hypothalamus, Posterior
Locus Coeruleus
Pedunculopontine Tegmental Nucleus
Preoptic Area
Raphe Nuclei
Sleep Wake Disorders
Ventral Tegmental Area
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