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Brain Res Brain Res Rev. 2005 Nov;49(3):429-54.

Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus.

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1
Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby, Canada BC V5A 1S6. mistlber@sfu.ca

Abstract

Despite significant progress in elucidating the molecular basis for circadian oscillations, the neural mechanisms by which the circadian clock organizes daily rhythms of behavioral state in mammals remain poorly understood. The objective of this review is to critically evaluate a conceptual model that views sleep expression as the outcome of opponent processes-a circadian clock-dependent alerting process that opposes sleep during the daily wake period, and a homeostatic process by which sleep drive builds during waking and is dissipated during sleep after circadian alerting declines. This model is based primarily on the evidence that in a diurnal primate, the squirrel monkey (Saimiri sciureus), ablation of the master circadian clock (the suprachiasmatic nucleus; SCN) induces a significant expansion of total daily sleep duration and a reduction in sleep latency in the dark. According to this model, the circadian clock actively promotes wake but only passively gates sleep; thus, loss of circadian clock alerting by SCN ablation impairs the ability to sustain wakefulness and causes sleep to expand. For comparison, two additional conceptual models are described, one in which the circadian clock actively promotes sleep but not wake, and a third in which the circadian clock actively promotes both sleep and wake, at different circadian phases. Sleep in intact and SCN-damaged rodents and humans is first reviewed, to determine how well the data fit these conceptual models. Neuroanatomical and neurophysiological studies are then reviewed, to examine the evidence for direct and indirect interactions between the SCN circadian clock and sleep-wake circuits. Finally, sleep in SCN-ablated squirrel monkeys is re-examined, to consider its compatibility with alternative models of circadian regulation of sleep. In aggregate, the behavioral and neurobiological evidence suggests that in rodents and humans, the circadian clock actively promotes both wake and sleep, at different phases of the circadian cycle. The hypersomnia of SCN-ablated squirrel monkeys is unique in magnitude, but is not incompatible with a role for the SCN pacemaker in actively promoting sleep.

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