4 years ago

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

Zhi-Li Huang, Wei-Min Qu, Su-Rong Yang, Yoan Cherasse, Michael Lazarus, Serge N Schiffmann, Rui-Xi Li, Hui Dong, Xiang-Shan Yuan, Lu Wang, Alban de Kerchove d'Exaerde
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.

Publisher URL: https://elifesciences.org/articles/29055

DOI: 10.7554/eLife.29055

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