神经网络示踪新技术及其在嗅觉神经环路特异受体探查中的应用

神经环路水平的功能异常和病变在神经系统疾病（尤其是精神疾病）的病理发生及临床表现中有重要作用。对疾病相关神经环路/网络在分子、解剖和功能水平上更深入全面地了解在发展神经系统疾病治疗的新机制和新药物的实践中有非常重要的作用。为了达到在分子和解剖的水平上更好地描述和解析神经环路/网络的目标，本项目将构建基于嗜神经性伪狂犬病毒（PRV)的高选择性神经网络示踪新技术，并将其应用于描述疾病相关神经网络并探查嗅觉神经环路中与本能生理反应有关的特异嗅觉受体。本项目拟进行的研究包括：1）构建新一代基于“FLEx”选择体制的多级PRV示踪工具；2）在体验证新PRV示踪工具的选择性和有效性并解析下丘脑重要神经元亚型的上游神经环路；3）利用新示踪工具探查GnRH神经元上游的特异嗅觉受体。本研究将开发出新的高选择性神经示踪工具并推进利用此新工具对疾病相关神经环路分子和功能特异性进行解析。

Dysregulation and malfunction of neural circuits play important roles in the pathogenesis of nervous system diseases (especially mental disorders) and manifestation of their symptoms. Development of new therapeutic strategies and new drugs for these devastating diseases demands a more comprehensive understanding of the molecular, anatomical, and functional properties of neural circuits/networks involved in these disorders. To achieve the goal of better describing and analyzing the molecular and anatomical characteristics of neural circuits/networks, we propose to develop PRV-based high-selectivity neural network tracing technology to facilitate the analyses of disease-related neural networks and identify olfactory receptors involved in regulation of distinct innate physiological responses. Proposed research includes: (1) Develop new-generation “FLEx”-based polysynaptic PRV tracers; (2) In vivo confirmation of PRV tracing activity and selectivity and analyze neural input networks for hypothalamic functional centers; (3) Isolate olfactory receptors that send input to hypothalamic GnRH neurons. These studies will develop novel high-specificity tracers and promote investigation of molecular and functional features of disease-related neural circuits/networks.