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Hypothalamic regulation of sleep and circadian rhythms

Abstract

A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal system during sleep. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioural states, such as occurs in narcolepsy. These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake–sleep cycles into the optimal pattern for survival.

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Figure 1: A drawing of the human brainstem, taken from von Economo's original work.
Figure 2: A schematic drawing showing some key components of the ascending arousal system.
Figure 3: A schematic drawing to show the key projections of the ventrolateral preoptic nucleus (VLPO) to the main components of the ascending arousal system.
Figure 4: A schematic diagram of the flip-flop switch model.
Figure 5: A schematic diagram to illustrate the three-stage integrator for circadian rhythms.

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This work was supported by United States Public Health Service grants.

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The authors declare competing financial interests: Dr Saper is a consultant for Sepracor, Inc and Merck, Inc. Dr Thomas Scammell is a consultant for Cephalon Inc and Orphan Medical Inc.

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Saper, C., Scammell, T. & Lu, J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257–1263 (2005). https://doi.org/10.1038/nature04284

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