Striatal adenosine A 2A  receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus

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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 A _2A receptors (A _2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A _2AR 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 A _2AR 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 A _2AR neurons. In addition, chemogenetic inhibition of striatal A _2AR 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 A _2AR neuron/GPe PV neuron circuit in sleep control.

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Author and article information

Contributors

Rui-Xi Li

Zhi-Li Huang:

ORCID: https://orcid.org/0000-0001-9359-1150

Louis J Ptáček: Role: Reviewing Editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic, pub): 12 October 2017

Publication date Collection: 2017

Volume: 6

Electronic Location Identifier: e29055

Affiliations

[1 ]deptDepartment of Pharmacology, School of Basic Medical Science Fudan University ShanghaiChina

[2 ]deptState Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science Fudan University ShanghaiChina

[3 ]deptDepartment of Anatomy, Histology and Embryology, School of Basic Medical Science Fudan University ShanghaiChina

[4 ]deptInternational Institute for Integrative Sleep Medicine University of Tsukuba TsukubaJapan

[5 ]deptLaboratory of Neurophysiology, ULB Neuroscience Institute Université Libre de Bruxelles BrusselsBelgium

University of California, San Francisco United States

Author notes

[†]

These authors contributed equally to this work.

Author information

Michael Lazarus https://orcid.org/0000-0003-3863-4474

Zhi-Li Huang https://orcid.org/0000-0001-9359-1150

Article

Publisher ID: 29055

DOI: 10.7554/eLife.29055

PMC ID: 5655138

PubMed ID: 29022877

SO-VID: e07054b3-f832-41d8-b179-1c8a409744fa

License:

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