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Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus

  1. Xiang-Shan Yuan
  2. Lu Wang
  3. Hui Dong
  4. Wei-Min Qu
  5. Su-Rong Yang
  6. Yoan Cherasse
  7. Michael Lazarus
  8. Serge N Schiffmann
  9. Alban de Kerchove d'Exaerde
  10. Rui-Xi Li  Is a corresponding author
  11. Zhi-Li Huang  Is a corresponding author
  1. Fudan University, China
  2. University of Tsukuba, Japan
  3. Université Libre de Bruxelles, Belgium
Research Article
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Cite this article as: eLife 2017;6:e29055 doi: 10.7554/eLife.29055

Abstract

Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2AR neuron/GPe PV neuron circuit in sleep control.

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Author details

  1. Xiang-Shan Yuan

    Department of Pharmacology, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Lu Wang

    Department of Pharmacology, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Hui Dong

    Department of Pharmacology, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Wei-Min Qu

    Department of Pharmacology, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Su-Rong Yang

    Department of Pharmacology, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Yoan Cherasse

    International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.

  7. Michael Lazarus

    International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3863-4474

  8. Serge N Schiffmann

    Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.

  9. Alban de Kerchove d'Exaerde

    Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.

  10. Rui-Xi Li

    Department of Pharmacology, Fudan University, Shanghai, China
    For correspondence
    ruixilee@shmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  11. Zhi-Li Huang

    Department of Pharmacology, Fudan University, Shanghai, China
    For correspondence
    huangzl@fudan.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9359-1150

Funding

National Natural Science Foundation of China (81420108015)

  • Zhi-Li Huang

National Natural Science Foundation of China (31671099)

  • Wei-Min Qu

National Natural Science Foundation of China (81271466)

  • Rui-Xi Li

National Natural Science Foundation of China (31571103)

  • Lu Wang

National Natural Science Foundation of China (81571296)

  • Su-Rong Yang

National Basic Research Program of China (2015CB856401)

  • Zhi-Li Huang

Shanghai Committee of Science and Technology (14JC1400900)

  • Zhi-Li Huang

National Natural Science Foundation of China (31471064)

  • Wei-Min Qu

National Natural Science Foundation of China (31530035)

  • Zhi-Li Huang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal studies were performed in accordance with protocols approved by the Committee on the Ethics of Animal Experiments of Fudan University Shanghai Medical College (permit number: 20110307-049). Every effort was made to minimize the number of animals used and any pain and discomfort experienced by the subjects.

Reviewing Editor

  1. Louis J Ptáček, University of California, San Francisco, United States

Publication history

  1. Received: May 29, 2017
  2. Accepted: October 11, 2017
  3. Accepted Manuscript published: October 12, 2017 (version 1)
  4. Version of Record published: October 24, 2017 (version 2)

Copyright

© 2017, Yuan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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