A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States.
A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States.
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DOI：
10.1016/j.neuron.2016.01.007
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发表时间：
2016-02-17
期刊：
影响因子：
16.2
通讯作者：
Prober DA
中科院分区：
文献类型：
--
作者：
Chiu CN;Rihel J;Lee DA;Singh C;Mosser EA;Chen S;Sapin V;Pham U;Engle J;Niles BJ;Montz CJ;Chakravarthy S;Zimmerman S;Salehi-Ashtiani K;Vidal M;Schier AF;Prober DA
唤醒状态的神经调节确保动物对其环境做出适当的反应，并参与生存所必需的行为。然而，睡眠和觉醒等觉醒状态的神经调节背后的分子和电路特性仍不清楚。为了以系统和公正的方式应对这一挑战，我们进行了基因过表达筛选，以确定影响斑马鱼幼鱼觉醒的基因。我们发现，神经肽neuromedin U（NMU）促进活动过度，抑制斑马鱼幼虫的睡眠，而NMU突变动物活动减退。我们发现，Nmu诱导的觉醒需要Nmu受体2和信号通过促肾上腺皮质激素释放激素（Crh）受体1。与以前提出的模型相反，我们发现NMU不通过下丘脑-垂体-肾上腺轴促进唤醒，而是可能通过脑干CRH表达神经元起作用。这些结果揭示了Nmu系统和脑干唤醒系统之间意想不到的功能和解剖界面，代表了一种新的唤醒促进途径。
Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotrophin-releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather likely acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.