瘙痒传染的视觉传入神经机制研究

In the recent Science paper, we reported contagious itch model in mice and discover the roles of the signaling pathway of gastrin-releasing peptide (GRP)and its receptor in the suprachiasmatic nucleus (SCN). However, the complete neural circuit mediating contagious itch is not fully understood. One of important scientific question to be answered is how the visual information of contagious itch is sent to SCN and further palys roles on the functions of SCN neurons. In the present project, we will focus on melanopsin neurons in retina and reveal the contributions of these neurons in the visual input of contagious itch. Combination of diverse techniques including behaviors,electrophysiological recordings,virus injections and tracing,optogenetic approaches,present research project would get further unstanding on the complete neural circuits of contagious itch and cellular mechanisms. The study will provide novel reference on the biologiacl function and significance of social contagious behaviors.

我们最近在Science杂志报道了瘙痒传染的小鼠模型，并揭示视交叉上核(suprachiasmatic nucleus，SCN)内胃泌素释放肽(GRP)及其受体神经环路的重要作用。然而目前对瘙痒传染的完整神经回路还不明确，其中一个尚未解决的重要的科学问题是瘙痒传染的视觉信息如何传递到SCN并进一步影响神经元功能。本项目将在前期已经发表工作和预实验的基础上，进一步以视网膜melanopsin神经元为靶点，运用行为学、电生理记录、病毒束路追踪、光遗传学，结合转基因动物，深入揭示瘙痒传染的视觉传入神经机制。该研究将进一步完善瘙痒传染的神经环路和细胞机制，为揭示社会行为传染的生物学功能和意义提供重要参考。

目前对瘙痒传染的完整神经回路还不明确，其中一个尚未解决的重要的科学问题是瘙痒传染的视觉信息如何传递到SCN并进一步影响神经元功能。本研究运用生物毒素saporin和行为学发现了特异性消除melanopsin神经元对瘙痒传染的影响；运用膜片钳、光/化学遗传学方法发现了melanopsin神经末梢激活对突触后电流IPSCs的影响；运用膜片钳、光/化学遗传学方法发现了melanopsin神经末梢激活对SCN神经元兴奋性的影响；运用膜片钳和药理学，发现了GABAA受体对SCN神经元IPSCs和兴奋性的影响；运用光遗传学激活melanopsin神经元诱发瘙痒行为。这些研究结果表明：视网膜melanopsin神经元是参与瘙痒传染的重要视觉机制之一。本研究将进一步完善瘙痒传染的神经环路和细胞机制，为揭示社会行为传染的生物学功能和意义提供重要参考。