Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus
- Fudan University, China
- University of Tsukuba, Japan
- Université Libre de Bruxelles, Belgium
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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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.
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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Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus
eLife 6:e29055.
https://doi.org/10.7554/eLife.29055
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