Abstract: The basal ganglia (BG) act as a cohesive functional unit that regulates motor function, habit formation, and reward/addictive behaviors. However, it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve all these fundamental functions until genetically engineered systems developed these years. We focused on the adenosine A2A and dopamine D1 Receptors (R) in the BG and obtained following 4 findings: (1) Nucleus accumbens (NAc) dopamine D1R-expressing neurons are essential in controlling wakefulness and are involved in physiological arousal via the lateral hypothalamus and midbrain circuits; (2) The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system and other regions. Our findings reveal an essential role of the RMTg in the promotion of non-rapid eye movement (non-REM, NREM) sleep and homeostatic regulation; (3) Opposite to the D1R in the NAc, A2AR made a prominent contribution to sleep control associated with motivation. (4) Striatal adenosine A2AR neurons control active-period sleep via parvalbumin neurons in external globus pallidus. Taken together, we proposed a plausible model in which the caudate-putamen and NAc integrate behavioral processes with sleep/wakefulness through adenosine and dopamine receptors. The impacts of the BG in physiological sleep and insomnia will be discussed.

Key words: adeno-associated virus, optogenetics, DREADD, basal ganglia, sleep-wake regulation