The Neurobiology of Sleep and Wakefulness

Cortical electroencephalographic activity arises from corticothalamocortical interactions, modulated by wake-promoting monoaminergic and cholinergic input. These wake-promoting systems are regulated by hypothalamic hypocretin/orexins, while GABAergic sleep-promoting nuclei are found in the preoptic area, brainstem and lateral hypothalamus. Although pontine acetylcholine is critical for REM sleep, hypothalamic melanin-concentrating hormone/GABAergic cells may gate REM sleep. Daily sleep-wake rhythms arise from interactions between a hypothalamic circadian pacemaker and a sleep homeostat whose anatomical locus has yet to be conclusively defined. Control of sleep and wakefulness involves multiple systems, each of which presents vulnerability to sleep/wake dysfunction that may predispose to physical and/or neuropsychiatric disorders.