A subset of cholinergic mushroom body neurons requires Go signaling to regulate sleep in Drosophila.
A subset of cholinergic mushroom body neurons requires Go signaling to regulate sleep in Drosophila.
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DOI：
10.5665/sleep.3206
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发表时间：
2013-12
期刊：
影响因子：
5.6
通讯作者：
W. Yi;Yunpeng Zhang;Yinjun Tian;Jing Guo;Yan Li;A. Guo
中科院分区：
文献类型：
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作者：
W. Yi;Yunpeng Zhang;Yinjun Tian;Jing Guo;Yan Li;A. Guo
确定睡眠调节的神经化学和神经回路对于理解睡眠和各种睡眠障碍至关重要。果蝇的睡眠行为与脊椎动物的睡眠行为具有相似性。在果蝇的中枢脑中，蘑菇体（MB）被强调为睡眠中心;然而，其神经化学性质仍不清楚，它是否促进睡眠或唤醒仍然是一个有争议的话题。设计：采用录像系统准确监测受试者的自主活动和睡眠状态。通过热诱导和Gal 4/UAS系统在时间和区域上操纵基因表达。我们发现，通过c309-Gal 4在MB中表达百日咳毒素（PTX）以阻断Go活性导致独特的睡眠缺陷，如白天睡眠急剧增加和夜间睡眠片段化。我们将表达c309-Gal 4的脑区域缩小到负责Go介导的睡眠效应的MB α/β核心神经元。利用神经递质特异性Gal 80基因工具和RNA干扰技术抑制乙酰胆碱信号，我们证明这些MB α/β核心神经元是胆碱能和睡眠促进神经元，支持Go介导抑制信号。有趣的是，我们发现相邻的MB α/β神经元也是胆碱能但促进唤醒的神经元，其中也需要Go信号。结论在果蝇中发现一组睡眠促进神经元被一组唤醒促进神经元包围。这两组神经元都是胆碱能神经元，使用Go抑制信号来调节睡眠。
STUDY OBJECTIVES 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. DESIGN 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. MEASUREMENTS AND RESULTS 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. CONCLUSION 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.