Yi Wei, Zhang Yunpeng, Tian Yinjun, Guo Jing, Li Yan, Guo Aike
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ; University of Chinese Academy of Sciences, Beijing, China.
Sleep. 2013 Dec 1;36(12):1809-21. doi: 10.5665/sleep.3206.
Identifying the neurochemistry and neural circuitry of sleep regulation is critical for understanding sleep and various sleep disorders. Fruit flies display sleep-like behavior, sharing essential features with sleep of vertebrate. In the fruit fly's central brain, the mushroom body (MB) has been highlighted as a sleep center; however, its neurochemical nature remains unclear, and whether it promotes sleep or wake is still a topic of controversy.
We used a video recording system to accurately monitor the locomotor activity and sleep status. Gene expression was temporally and regionally manipulated by heat induction and the Gal4/UAS system.
We found that expressing pertussis toxin (PTX) in the MB by c309-Gal4 to block Go activity led to unique sleep defects as dramatic sleep increase in daytime and fragmented sleep in nighttime. We narrowed down the c309-Gal4 expressing brain regions to the MB α/β core neurons that are responsible for the Go-mediated sleep effects. Using genetic tools of neurotransmitter-specific Gal80 and RNA interference approach to suppress acetylcholine signal, we demonstrated that these MB α/β core neurons were cholinergic and sleep-promoting neurons, supporting that Go mediates an inhibitory signal. Interestingly, we found that adjacent MB α/β neurons were also cholinergic but wake-promoting neurons, in which Go signal was also required.
Our findings in fruit flies characterized a group of sleep-promoting neurons surrounded by a group of wake-promoting neurons. The two groups of neurons are both cholinergic and use Go inhibitory signal to regulate sleep.
确定睡眠调节的神经化学和神经回路对于理解睡眠及各种睡眠障碍至关重要。果蝇表现出类似睡眠的行为，与脊椎动物的睡眠具有基本特征。在果蝇的中枢大脑中，蘑菇体（MB）已被视为睡眠中心；然而，其神经化学性质仍不清楚，它是促进睡眠还是觉醒仍是一个有争议的话题。
我们使用视频记录系统精确监测运动活动和睡眠状态。通过热诱导和Gal4/UAS系统在时间和区域上操纵基因表达。
我们发现，通过c309-Gal4在蘑菇体中表达百日咳毒素（PTX）以阻断Go活性，会导致独特的睡眠缺陷，即白天睡眠显著增加，夜间睡眠碎片化。我们将c309-Gal4表达的脑区缩小到负责Go介导的睡眠效应的蘑菇体α/β核心神经元。使用神经递质特异性Gal80的遗传工具和RNA干扰方法来抑制乙酰胆碱信号，我们证明这些蘑菇体α/β核心神经元是胆碱能且促进睡眠的神经元，支持Go介导抑制性信号。有趣的是，我们发现相邻的蘑菇体α/β神经元也是胆碱能但促进觉醒的神经元，其中Go信号也是必需的。
我们在果蝇中的发现确定了一组促进睡眠的神经元被一组促进觉醒的神经元所包围。这两组神经元都是胆碱能的，并利用Go抑制信号来调节睡眠。
