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

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(2A)Rs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A(2A)R 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(2A)R 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(2A)R neurons. In addition, chemogenetic inhibition of striatal A(2A)R 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(2A)R neuron/GPe PV neuron circuit in sleep control.