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  • States of sleep and wakefulness are both active processes mediated by specific brain regions and neurotransmitter systems.

  • Drowsiness is a state of diminished vigilance that occurs in transitions between wake and sleep. Sleep itself can be divided into two phases, nonrapid eye movement (nonREM) and REM sleep, the latter being characterized by brain activity resembling that observed during the waking state.

  • The physiologic functions of distinct phases of sleep are unknown. Overall, the timing and quality of sleep may play important roles in memory consolidation and metabolic processes.

  • The initiation of nonREM 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 in the brainstem. Many additional nuclei contribute to the regulation of sleep and wake time.

  • 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 and mortality.

  • Narcolepsy is a sleep disorder characterized by abnormal regulation of sleep–wake cycles. Most cases are caused by the autoimmune destruction of the brain’s orexin–containing neurons in the lateral hypothalamus.

  • Benzodiazepines and similarly acting drugs, which are positive allosteric modulators of GABAA receptors, are the most common pharmacologic treatments for insomnia. Orexin receptor antagonists are a more recently introduced class of anti-insomnia medications.

  • General anesthetics, comprising diverse classes of compounds, induce a transient coma that resembles nonREM sleep electrophysiologically, and is clinically characterized by global amnesia, analgesia, and nonresponsiveness. Most general anesthetics act, at least in part, by facilitating inhibitory ion channels (including ligand–gated channels) or inhibiting excitatory ion channels.

The first part of this chapter presents a broad overview of the neurobiology of sleep and arousal states. The second part covers certain major sleep disorders, the mechanisms of which continue to be elucidated. The third part discusses the pharmacologic treatment of these disorders.

As with other behavioral states, the initiation and maintenance of wakefulness and specific sleep states, such as rapid eye movement (REM) and nonrapid eye movement (NREM) sleep, are governed by changes in the activity of specific neural circuits. These circuits can be disrupted in many ways, giving rise to a multitude of disorders that impact the quality or quantity of sleep. 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 sleep behavior disorder display episodes where they “act out their dreams” and may ...

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