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Brain Research Reviews
Volume 49, Issue 3 , November 2005, Pages 429-454
Circadian regulation of sleep in mammals: Role of the suprachiasmatic
nucleus
Ralph E. Mistlberger,
Department of Psychology, Simon Fraser University, 8888 University
Drive, Burnaby, Canada BC V5A 1S6
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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