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The role of co-neurotransmitters in sleep and wake regulation

Molecular Psychiatry volume 24, pages 1284–1295 (2019)Cite this article

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Abstract

Sleep and wakefulness control in the mammalian brain requires the coordination of various discrete interconnected neurons. According to the most conventional sleep model, wake-promoting neurons (WPNs) and sleep-promoting neurons (SPNs) compete for network dominance, creating a systematic “switch” that results in either the sleep or awake state. WPNs and SPNs are ubiquitous in the brainstem and diencephalon, areas that together contain <1% of the neurons in the human brain. Interestingly, many of these WPNs and SPNs co-express and co-release various types of the neurotransmitters that often have opposing modulatory effects on the network. Co-transmission is often beneficial to structures with limited numbers of neurons because it provides increasing computational capability and flexibility. Moreover, co-transmission allows subcortical structures to bi-directionally control postsynaptic neurons, thus helping to orchestrate several complex physiological functions such as sleep. Here, we present an in-depth review of co-transmission in hypothalamic WPNs and SPNs and discuss its functional significance in the sleep–wake network.

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Acknowledgements

We gratefully acknowledge support from the Tau Consortium/Rainwater Charitable Foundation and NIH grants: K24AG053435 (LTG), R56MH107042 (TCN). The Grants that support JCB came from the Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation - FAPESP] grant #2016/02224-1 [JCB], the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [Agency for the Advancement of Higher Education – CAPES grant #848/15], and the Conselho Nacional de Desenvolvimento Científico e Tecnológico [National Council for Scientific and Technological Development - CNPq] with grant #426378/2016-4. JCB is an investigator with the CNPq. JYO is a Tau Consortium Fellow. We also thank Dulce Morales for histology and Evan T. Keum and Brian Hitchin for manuscript editing.

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Authors and Affiliations

  1. Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA

    Jun Oh, Cathrine Petersen, Christine M. Walsh & Lea T. Grinberg

  2. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA

    Jun Oh & Cathrine Petersen

  3. Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Jackson C. Bittencourt

  4. Center for Neuroscience and Behavior, Institute of Psychology, University of Sao Paulo, Sao Paulo, Brazil

    Jackson C. Bittencourt

  5. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA

    Thomas C. Neylan

  6. Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil

    Lea T. Grinberg

  7. Department of Pathology, University of California, San Francisco, San Francisco, CA, USA

    Lea T. Grinberg

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  1. Jun Oh
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Correspondence to Lea T. Grinberg.

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Oh, J., Petersen, C., Walsh, C.M. et al. The role of co-neurotransmitters in sleep and wake regulation. Mol Psychiatry 24, 1284–1295 (2019). https://doi.org/10.1038/s41380-018-0291-2

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  • DOI: https://doi.org/10.1038/s41380-018-0291-2

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