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Both sleep and arousal are active processes mediated by specific brain regions and neurotransmitter systems.
Sleep can be divided into two phases, nonrapid eye movement (non-REM) and REM sleep, the latter being characterized by brain activity resembling that observed during the waking state.
The different physiologic functions of sleep are unknown; a role in memory consolidation is likely.
The initiation of non-REM sleep is controlled in part by GABAergic neurons in the preoptic/anterior hypothalamic area; the initiation of REM sleep is controlled by cholinergic cells in the pontine tegmentum.
Sleep is controlled both by circadian rhythms and by the homeostatic drive produced by periods of wakefulness. Adenosine is an important mediator of the homeostatic drive for sleep.
The suprachiasmatic nucleus is the primary pacemaker for the circadian regulation of sleep and other physiologic processes, in particular, for entraining circadian rhythms to environmental light.
Circadian rhythms are produced, in part, by the complex transcriptional regulation of “clock” genes that have been conserved throughout evolution.
Sleep disorders are a significant cause of morbidity. A major advance is the finding that decreased expression of the hypothalamic neuropeptide orexin (also called hypocretin) causes most human narcolepsy.
Benzodiazepines and similarly acting drugs, which are positive allosteric modulators of GABAA receptors, are the most common pharmacologic treatments for insomnia.
General anesthetics, comprising diverse classes of compounds, induce a non-REM sleep-like state characterized by amnesia, analgesia, immobility, and hypnosis. Most general anesthetics act, at least in part, by facilitating inhibitory ion channels (including ligand-gated channels) or inhibiting excitatory ion channels.
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Defining sleep and arousal is not a simple matter. Sleep is clearly different from hibernation, coma, or states produced by general anesthesia. The first part of this chapter presents a broad overview of the neurobiology of sleep and arousal states. The second part covers some of the major sleep disorders, the mechanisms of which are slowly being elucidated. The third part discusses the pharmacologic treatment of these disorders.
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As with other behavioral states such as fear and reward (Chapters 15 and 16), sleep states, such as rapid eye movement (REM) and nonrapid eye movement (NREM) sleep, depend on specific neural circuits. However, certain phenomena that occur during sleep may also employ some of the circuitry that contributes to behavioral states during waking hours. Night terrors, for example, involve a partial arousal out of deep NREM sleep; patients exhibit powerful sympathetic activation including tachycardia, mydriasis, and diaphoresis, despite the fact that they remain asleep. In contrast, patients with REM behavior disorder may have bouts of violent behavior during REM sleep that are not accompanied by elevations in heart rate or blood pressure. Hence, states of sleep and arousal are complex and heterogeneous and cannot be explained by a simple rheostat model.
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Before the beginning of the 20th century, sleep was conceptualized as a passive process; ...