主副嗅系统的回路结构及两者之间的关系

The main and accessory olfactory systems are important pathways to sense the environment and mediate social behaviors. Classical hypothesis is that: the main olfactory system is for detection of general odors, whereas the accessory, for pheromones, and the two neural pathways for transferring information seem to be parallel to each other. However, recent evidences, including studies from our lab, show that the two olfactory systems have more cross-talks than previously thought, even mutual regulations. Because the anatomical relationship between the two systems is unclear, the corresponding functional mechanisms can never been elucidated. This project plans to use a variety of neurocircuit tracing neurotropic viral systems that can spread along synaptic connections anterogradely or retrogradely with contrallable labeling range (trans-mono-, or trans-multi-synapses), and combine with a variety of cell type-specific transgenic mice (such as, cre-lines), to reveal the global input and output networks of the main and accessory olfactory systems, as well as the fine neurocircuits of different cell types in the main and accessory olfactory bulbs, and then through detailed analysis to map out the structural relationships between the two olfactory systems. The results from the project will lay fundation for future studies on the functions of either system, or the interactions between the two systems.

主嗅和副嗅系统是感知外界和调控社会行为的重要途径。传统的研究认为主嗅感知普通气味，副嗅感知信息素，且信息传递的通路互相平行、相对独立。但最近的研究，包括申请人实验室的工作，揭示了主、副嗅具有远超过预期的功能重叠，甚至可能存在互相调控，但相应的神经解剖基础几乎未知。本项目拟利用实验室建立的多种顺向和逆向跨单级和多级突触的嗜神经工具病毒回路标记体系，结合各种细胞类型特异性的转基因小鼠，绘制完整的小鼠主、副嗅系统的输入和输出网络，以及嗅球和副嗅球内的各种细胞特异性的精细回路；通过整合分析揭示主、副嗅之间的结构关系，为将来进一步阐明主副嗅的功能关系以及在社会行为中的协同作用提供结构基础。

本项目利用多种嗜神经工具病毒研究了主副嗅的神经网络以及相互关系。利用逆行跨多级突触的伪狂犬病毒（PRV152）在小鼠嗅球（OB）的多级调控网络标记中发现副嗅球（AOB）可以被感染上，表明AOB的一级向心投射脑区可能调控OB；利用轴突末端吸收的染料（CTB）、缺失膜蛋白的狂犬病毒（RV-dG-EGFP）以及RetroAAV，共同确定了小鼠AOB的一级向心投射网络包括但不限于：BNSTMA、PLCO、PMCO、BAOT、MeA、MePD和MePV，并发现PLCO可能共同接受OB和AOB的向心输入，表明主、副嗅信息可能汇聚于此；另外，利用双色RetroAAV同时标记不同副嗅皮层后逆行在AOB汇聚重叠证明AOB的投射神经元向心一级投射具有轴突分支现象；此外，AOB的一级向心输入脑区BNSTMA神经元轴突可以投射到OB的GCL，表明AOB可能通过BNSTMA调控OB的气味感知。