狂犬病病毒（RABV）感染引起严重的神经功能异常表征，但其机制尚不明确。我们前期研究发现，RABV感染导致Rac1活性下调，F-actin荧光强度降低。由于Rac1与细胞骨架动态变化密切相关，为此，本项目拟以Rac1活性为切入点，研究RABV感染对F-actin骨架形成、突触囊泡募集、树突棘形态及突触电位等的影响，并对Rac1-PAK信号通路的关键分子表达及其磷酸化水平进行检测，以阐释RABV抑制F-actin聚合及突触功能的分子机制。这一研究对于解析RABV致突触功能异常的机制具有重要意义，同时Rac1类调节剂也有望为狂犬病临床治疗和靶向药物开发提供方向。

It is well established that neuronal dysfunction may be responsible for the development of rabies，the mechanism of which remains unclear. Our previous research revealed that Rac1 was remarkably inactivated after RABV infection, as well as the fluorescence intensity of F-actin impaired. Based on the research that Rac1 plays a pivotal role in synaptic function through modulating F-actin dynamics, the project will focus on RABV dyregulating the activity of Rac1. After RABV infection, we firstly demonstrate aberrant actin polymerization; secondly, we attempt to detect the alteration of synaptic vesicles clustering and dendritic spine morphogenesis, as well as action potential; thirdly, we try to detect the expression and phosphorylation of key molecules involved in Rac1-PAK signaling pathway; Finally, we elucidate the mechanism of which RABV infection influences synaptic function through downregulating Rac1 activity and obstructing actin cytoskeleton reorganization. It is helpful to further contribute to our understanding of the pathogenesis of rabies, and might be theoretical basis for rabies clinical therapy and drug development.