Roles of the basal ganglia in physiological sleep-wake cycles and sleep disorders of Parkinson's disease

摘要

Roles of the basal ganglia in physiological sleep-wake cycles and sleep disorders of Parkinson’s disease Zhi-Li Huang*, Wei-Min Qu Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology; Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China Sleep disorders are frequent in Parkinson’s disease (PD) and their prevalence increases with disease progression. Previous stud- ies demonstrated that sleep disorders could appear as an initial manifestation of PD even decades before motor signs, which high- light their clinical association in these early stages. Dysfunction of dopaminergic transmission in basal ganglia involves in the pathogenesis of PD and sleep disorders. 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 Aj, and dopamine D, receptors (R) in the BG and obtained following 4 findings: (1) Nucleus accumbens (NAc) dopamine D,R-expressing neurons are essential in controlling wakefulness and are involved in physiological arousal via the lateral hypothalamus and midbrain circuits; (2) The rostromedial tegmen- tal 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 DR in the NAc, AzaR made a prominent contribution to sleep control associ- ated 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 in Parkinson's patients will be discussed.