癫痫是以复发性癫痫发作为特征的常见病。癫痫的发病与海马关系极为密切。癫痫模型诱发海马神经元发生、发育、迁移异常。因此推测，这些异常新生神经元的环路构建异常并且是癫痫发作病理形成的关键基础。本项目将运用国际先进的环路追踪方法（逆转录病毒-狂犬病毒双病毒逆行追踪神经元环路系统、WGA顺行追踪神经元环路系统）鉴定癫痫模型诱导的海马新生神经元环路异常构建的动态过程。结合特异性阻断、激活或抑制神经环路的转基因小鼠和病毒模型（NCE：YY；iDTR系统、POMC-Cre；Dreadds系统）和split cre系统鉴定海马新生神经元特定异常环路在癫痫中的角色。另外，将鉴定介导癫痫环路异常构建的分子机制，试图通过操控靶分子重塑海马新生神经元异常环路、治疗癫痫发作。通过上述研究，本项目将阐明海马新生神经元的环路构建在癫痫发作与治疗中的作用，为深入理解癫痫病理机制和新治疗靶点开发作出极大的推动。

Epilepsy, a common disorder characterized by recurrent seizures. The hippocampus correlates closely with the pathology of epilepsy. Aberrant neurogenesis，neural develop，and migration are observed in the hippocampus. Therefore, we speculate that these abnormal new neurons format aberrant circuit and play a crucial role in the pathology of epilepsy. Here, we are going to use the advanced tracing system (retrograde tracing based on dual viruses, retrovirus-rabies; antegrade tracing based on WGA system) to identify dynamic formation of the aberrant circuit of hippocampal newborn neurons in epilepsy model. Meanwhile, in combination with the transgenic and viral methods (NCE：YY；iDTR model, POMC-Cre；Dreadds model) for blockade, stimulation, and inhibition of certain circuit, and split cre system, we will illustrate the relationship between the circuit and the pathology of epilepsy. In addition, we are going to screen the molecular mechanism underlying the formation of the aberrant circuit and then induce reconstruction of the abnormal circuit via operating target molecular to cure epilepsy. In this study, we will reveal the critical role of aberrant circuit of the hippocampal new neurons in the development of the pathology of epilepsy, providing new insights into the mechanisms and the therapy of epilepsy.