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Neuro-orchestration of sleep and wakefulness

Nature Neuroscience volume 26, pages 196–212 (2023)Cite this article

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Abstract

Although considered an inactive state for centuries, sleep entails many active processes occurring at the cellular, circuit and organismal levels. Over the last decade, several key technological advances, including calcium imaging and optogenetic and chemogenetic manipulations, have facilitated a detailed understanding of the functions of different neuronal populations and circuits in sleep–wake regulation. Here, we present recent progress and summarize our current understanding of the circuitry underlying the initiation, maintenance and coordination of wakefulness, rapid eye movement sleep (REMS) and non-REMS (NREMS). We propose a de-arousal model for sleep initiation, in which the neuromodulatory milieu necessary for sleep initiation is achieved by engaging in repetitive pre-sleep behaviors that gradually reduce vigilance to the external environment and wake-promoting neuromodulatory tone. We also discuss how brain processes related to thermoregulation, hunger and fear intersect with sleep–wake circuits to control arousal. Lastly, we discuss controversies and lingering questions in the sleep field.

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Fig. 1: The orchestration of wakefulness.
Fig. 2: The orchestration of NREMS.
Fig. 3: The orchestration of REMS.

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Acknowledgements

The authors apologize that, owing to a limit on the number of references, primary papers could not be cited in some cases. Work in the Eban-Rothschild lab is supported by grants from the National Institutes of Health (1RF1MH120005-01 and R01 MH063649-17) and the Neuroscience Scholar Research Award (UM). B.A.S. is supported by the Rackham Regents Fellowship (UM).

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  1. Jean Tyan

    Present address: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

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  1. Department of Psychology, University of Michigan, Ann Arbor, MI, USA

    Bibi A. Sulaman, Su Wang, Jean Tyan & Ada Eban-Rothschild

  2. Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA

    Bibi A. Sulaman

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Sulaman, B.A., Wang, S., Tyan, J. et al. Neuro-orchestration of sleep and wakefulness. Nat Neurosci 26, 196–212 (2023). https://doi.org/10.1038/s41593-022-01236-w

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