Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Key Laboratory of Molecular Biophysics of Ministry of Education, Institute of Biophysics and Biochemistry, and Department of Biophysics and Molecular Physiology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Cell Rep. 2018 Nov 13;25(7):1885-1897.e9. doi: 10.1016/j.celrep.2018.10.065.
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 Cu stimulation. ASIs are inhibited in parallel by sensory neurons ASER, ADFs, and ASHs. ASER activates RIC interneurons 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 Cu 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 Cu stimulation. Our findings elucidate the molecular and circuit mechanisms regulating fundamental properties of ASIs, including their inhibition and delayed response.
在刺激过程中，使离反应神经元保持静止的机制在很大程度上是未知的。在这里，我们剖析了在伤害性 Cu 刺激期间抑制 ASI 神经元的离反应的潜在分子和电路机制。ASIs 被感觉神经元 ASER、ADFs 和 ASHs 平行抑制。ASER 激活 RIC 中间神经元，释放章鱼胺 (OA) 通过 SER-3 和 SER-6 受体抑制 ASIs。ADFs 释放 5-HT，作用于 SER-1 受体激活 RICs，随后抑制 ASIs。此外，即使所有抑制性神经元都被沉默，ASIs 也只被 Cu 刺激引发延迟的 ON 反应，这是 ASIs 的固有特性。在 ASIs 的纤毛中异位表达与 OSM-9 协同作用的离子通道 OCR-2，可在 Cu 刺激时立即诱导 ASIs 的 ON 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。
