癫痫是以大脑神经元异常放电引起反复痫性发作为特征的常见病，因其分子细胞机制并不完全明确，目前药物治疗尚难以治愈。海马齿状回颗粒细胞的结构和迁移异常、兴奋性神经环路构建过度与癫痫病理进程密切相关，但其分子机制不明。2019年Nature最新研究报道，小胶质细胞特异性表达的CD22，参与介导衰老大脑小胶质细胞吞噬功能的损伤；我们初步研究发现，癫痫齿状回小胶质细胞CD22异常表达上调，且与兴奋性突触蛋白表达上调正相关；因此本项目首次提出，CD22显著上调抑制小胶质细胞的吞噬功能，导致其对齿状回颗粒细胞兴奋性突触修剪的失败，使得兴奋性突触异常增多以及兴奋性神经环路构建增加，从而引发癫痫反复痫性发作。本项目拟运用双光子成像、活细胞工作站、病毒环路追踪等技术，阐明CD22介导的小胶质细胞调控齿状回颗粒细胞突触修剪异常、兴奋性神经环路构建紊乱的细胞间通讯机制，为癫痫研究提供新的理论思路和潜在的治疗靶点。

Epilepsy is a common disease characterized by recurrent epileptic seizures caused by abnormal discharge of brain neurons. Due to the unclear molecular mechanism of epilepsy, it is difficult to cure by drug therapy. The abnormal structure and migration of dentate gyrus granule cells in hippocampus, and the over construction of excitatory neural circuits are closely related to the pathological process of epilepsy, but the molecular mechanism is unknown. According to the latest report of Nature in 2019, CD22 specifically expressed on microglia is involved in the damaged microglial phagocytosis of aging brain. Our preliminary study found that CD22 expression of microglia in epileptic dentate gyrus is abnormally up-regulated, which had positive correlation with the up-regulated expression of excitatory synaptic proteins. Therefore, this project is the first to propose that significantly up-regulated CD22 inhibits microglial phagocytosis, leading to the failure of excitatory synapse pruning in dentate gyrus granule cells, which results in the abnormal increases of excitatory synapses and construction of excitatory neural circuits, thus causing recurrent epileptic seizures. This project intends to use two-photon imaging, live cell imaging system, virus-based neuronal network tracing and other technologies to clarify the mechanism of intercellular communication that CD22 mediated abnormally microglial synaptic pruning of dentate gyrus granule cells and disorderly construction of excitatory neural circuits, which provides a new theoretical thinking and a potential therapeutic strategy for epilepsy.