Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.
Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.
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DOI：
10.1016/j.cub.2015.09.017
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发表时间：
2015-11-16
期刊：
影响因子：
--
通讯作者：
Nitabach MN
中科院分区：
文献类型：
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作者：
Sitaraman D;Aso Y;Jin X;Chen N;Felix M;Rubin GM;Nitabach MN
果蝇蘑菇体（MB）是一个关键的联想记忆中心，也与睡眠控制有关。然而，MB神经元的身份基础稳态睡眠调节，以及由特定类别的MB神经元产生的睡眠信号的类型，仍然知之甚少。我们最近确定了两个MB输出神经元（MBON）类，其轴突从MB传递睡眠控制信号，以收敛在同一下游目标区域：胆碱能睡眠促进MBON类和多巴胺能唤醒促进MBON类。在这里，我们部署了神经遗传学，行为和生理方法的组合，以确定和机械解剖睡眠控制电路的MB。我们的研究揭示了存在两个分离的兴奋性突触微电路，其将稳态睡眠信息从不同群体的内在MB“凯尼恩细胞”（KCs）传播到特定的睡眠调节MBON：促进睡眠的KCs通过优先激活胆碱能MBON来增加睡眠，而促进觉醒的KCs通过优先激活多巴胺能MBON来减少睡眠。重要的是，睡眠促进MB微电路的活动通过睡眠剥夺而增加，并且是稳态反弹睡眠所必需的（即，在剥夺睡眠后增加的睡眠，并作为对剥夺睡眠的补偿）。这些研究首次揭示了KC亚群和特定MBON之间的特定功能连接，并建立了MB中稳态睡眠信号传输的突触微电路的身份。
The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB “Kenyon cells” (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB.