Xiang-Shan Yuan 1 , 2 , 3 , Lu Wang 1 , 2 , Hui Dong 1 , 2 , Wei-Min Qu 1 , 2 , Su-Rong Yang 1 , 2 , Yoan Cherasse 4 , Michael Lazarus 4 , Serge N Schiffmann 5 , Alban de Kerchove d'Exaerde 5 , Rui-Xi Li , 3 , Zhi-Li Huang , 1 , 2
12 October 2017
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.