The Neurobiology of Sleep

Clifford B. Saper, MD, PhD, FAAN, FRCP Sleep Disorders p. 19-31 February 2013, Vol.19, No.1 doi: 10.1212/01.CON.0000427215.07715.73
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Purpose of Review: 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.

Recent Findings: 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.

Summary: 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.

Address correspondence to Dr C. B. Saper, Department of Neurology, Beth Israel Deaconess Medical Center, 300 Brookline Avenue, Boston, MA 02215,

Relationship Disclosure: Dr Saper serves as Editor Emeritus for The Journal of Comparative Neurology.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Saper reports no disclosure.

© 2013 American Academy of Neurology