Abstract
The basic circuitries that regulate wake-sleep cycles are described, along with how these are affected by different disease states and how those alterations lead to the clinical manifestations of those disorders. The discovery of both sleep-promoting neurons in the ventrolateral preoptic nucleus and wake-promoting neurons, such as the lateral hypothalamic orexin (also called hypocretin) neurons, has allowed us to recognize that these two populations of neurons are mutually antagonistic (ie, inhibit each other) and form a "flip-flop switch," a type of circuit that results in rapid and complete transition in behavioral state. The same principle applies to the circuitry controlling transitions between REM sleep and non-REM (NREM) sleep. The flip-flop switch circuitry of the wake-sleep regulatory system produces the typical sleep pattern seen in healthy adults, with consolidated waking during the day and alternation between NREM and REM sleep at night. Breakdown in this circuitry both results in and explains the manifestations of a variety of sleep disorders including insomnia, narcolepsy with cataplexy, and REM sleep behavior disorder.
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