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Circadian regulation of sleep in mammals: Role of the suprachiasmatic nucleus
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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“The central clock of our brain is located in the hypothalamic suprachiasmatic nucleus (SCN) and drives many physiological and behavioral rhythms including the promotion of sleep during one part of the circadian cycle and wakefulness during the other part [59], in humans respectively night and day.”
From Sleep, vigilance, and thermosensitivity (2012) · cites this paper as [59]
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Neural Circuitry of Wakefulness and Sleep
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Metadata
- Authors
- Mistlberger, R. E.
- Affiliations
- Simon Fraser University (CA)
- Corresponding author
- Mistlberger, Ralph E.
- Venue
- Brain Research Reviews
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 49
- Issue
- 3
- Pages
- 429-454
- ISSN
- 0165-0173 (ISSN-L)
- OpenAlex
- W1984524952
- Cited by
- 318
- References
- 253
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 18 · 2018: 10 · 2017: 14 · 2016: 22 · 2015: 14 · 2014: 14 · 2013: 24 · 2012: 26
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- suprachiasmatic nucleus, circadian clock, sleep-wake regulation, sleep homeostasis, sleep drive, hypersomnia, squirrel monkey, circadian pacemaker
- MeSH terms
- Animals, Circadian Rhythm, Humans, Mammals, Sleep, Sleep Deprivation, Suprachiasmatic Nucleus, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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