Dissecting Molecular and Circuit Mechanisms for Inhibition and Delayed Response of ASI Neurons during Nociceptive Stimulus
Dissecting Molecular and Circuit Mechanisms for Inhibition and Delayed Response of ASI Neurons during Nociceptive Stimulus
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剖析伤害性刺激期间 ASI 神经元抑制和延迟反应的分子和电路机制。
DOI：
10.1016/j.celrep.2018.10.065
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发表时间：
2018-11-13
期刊：
影响因子：
8.8
通讯作者：
Dong, Zhiqiang
中科院分区：
文献类型：
--
作者：
Guo, Min;Ge, Minghai;Dong, Zhiqiang
关闭反应神经元在刺激期间保持静止的机制在很大程度上是未知的。在这里，我们剖析了潜在的分子和电路机制，在伤害性Cu 2+刺激过程中抑制关闭响应ASI神经元。ASIs被感觉神经元ASER、ADF和ASHs平行抑制。ASER通过SER-3和SER-6受体激活释放章鱼胺（OA）的RIC中间神经元以抑制ASI。ADF释放5-HT，其作用于SER-1受体以激活RIC并随后抑制ASI。此外，这是ASI的固有特性，即即使当所有抑制性神经元沉默时，Cu 2+刺激也仅诱发延迟的响应。与OSM-9协同作用的离子通道OCR-2在ASI的纤毛中的异位表达可以诱导ASI在Cu 2+刺激后的立即反应。我们的研究结果阐明了调节ASIs基本特性的分子和电路机制，包括它们的抑制和延迟反应。
The mechanisms by which off-response neurons stay quiescent during stimulation are largely unknown. Here, we dissect underlying molecular and circuit mechanisms for the inhibition of off-response ASI neurons during nociceptive Cu2+ stimulation. ASIs are inhibited in parallel by sensory neurons ASER, ADFs, and ASHs. ASER activates RIC inter-neurons that release octopamine (OA) to inhibit ASIs through SER-3 and SER-6 receptors. ADFs release 5-HT that acts on the SER-1 receptor to activate RICs and subsequently inhibit ASIs. Furthermore, it is an inherent property of ASIs that only a delayed on response is evoked by Cu2+ stimulation even when all inhibitory neurons are silenced. Ectopic expression of the ion channel OCR-2, which functions synergistically with OSM-9, in the cilia of ASIs can induce an immediate on response of ASIs upon Cu2+ stimulation. Our findings elucidate the molecular and circuit mechanisms regulating fundamental properties of ASIs, including their inhibition and delayed response.