睡眠障碍已成为日益严重的社会及医学问题，生理性睡眠-觉醒调节机制亟待阐明。我们发现基底神经节（BG）是参与睡眠-觉醒调控的重要结构，黑质致密部多巴胺（DA）能神经元毁损致背侧纹状体（CPu）去DA支配后，大鼠觉醒量显著增加；增强CPu DA的释放则促进大鼠睡眠。但DA被认为是促觉醒递质。我们推测不同DA能神经通路对睡眠-觉醒的调控作用相反，BG黑质纹状体通路的DA参与睡眠调控，而中脑边缘通路的DA促进觉醒。为验证这一假设，本题将采用化学遗传学、光遗传学技术，结合脑电记录、局部基因敲除、电生理及免疫组织化学等方法，通过特异调控BG DA黑质纹状体通路和中脑边缘通路观察其对睡眠-觉醒的影响，并进一步探讨BG DA能通路调控睡眠-觉醒的机制。研究结果将明确神经递质DA对睡眠-觉醒的影响，增添DA调控睡眠-觉醒的新机制，丰富和发展睡眠-觉醒调节理论，对探索临床治疗睡眠障碍具有重要意义。

Sleep disorder is an increasingly serious social and medical problem, while the mechanisms of physiological sleep-wake regulation are still unclear. Basal ganglia (BG) is important in regulating sleep and wakefulness, lesions of dopaminergic neurons located in substantia nigra pars compacta, result in dopamine (DA) de-innervation in dorsal striatum (CPu), and increase wakefulness in rats; while increase the release of DA in CPu results in sleep promotion. As DA is thought to be a wake-related neurotransmitter, we hypothesized that the different dopaminergic pathways may have opposite roles in sleep-wake regulation. To verify this hypothesis, we will apply a novel chemogenetic/optogenetic approach to selectively modulate the activity of nigrostriatal pathway and mesolimbic pathway in BG, to clarify the role of these two dopaminergic pathways in sleep-wake regulation; furthermore, By combining global or local gene knock down, and adopt a dopamine receptor D1 and D2 double gene reporter mice, to elucidate the mechanism of BG dopaminergic pathways in sleep-wake regulation. The results of the project will specific the influence of DA on sleep and wakefulness, bring contributions to the enrichment and development of sleep-wake regulation theory, and play an important role in exploring methods of treating sleep disorders.