常染色体显性侧颞叶癫痫（Autosomal Dominant Lateral Temporal Epilepsy，ADLTE）是一类家族遗传性神经系统疾病。ADLTE患者人群症状不一、常反复发病、药物治疗个体差异大。已知富含亮氨酸的胶质瘤失活基因1（leucine rich, glioma inactivated gene 1，LGI1）的突变与ADLTE密切相关，但不同LGI1突变导致ADLTE的机制尚不明确。现有研究认为分泌型LGI1具有生理功能，但申请人前期研究发现不分泌型LGI1，如LGI1W183R，也可以调节神经元兴奋性。据此本项目将综合利用膜片钳电生理、生物化学和分子生物学、病毒定位注射、基因快速置换和基因模式小鼠等技术，研究LGI1W183R等多个LGI1点突变在调节海马神经元兴奋性中的作用，明确其在ADLTE中的致病机制，并寻找相应的治疗靶点。

Autosomal Dominant Lateral Temporal Epilepsy (ADLTE) is a familial hereditary nervous system disease. ADLTE patients suffer from repeated seizures and have various drug’s efficacies. It is known that the mutations in leucine rich, glioma inactivated gene 1 (LGI1) are closely related to ADLTE, but the mechanisms of different LGI1 point mutations lead to ADLTE remain unclear. Secretary LGI1 has physiological functions, however our preliminary work showed that non-secretary LGI1W183R also exerts a role in regulating neuronal excitability. The present project will use patch clamp electrophysiology, biochemistry and molecular biology, virus injection, gene rapid replacement technology, and transgenic mice to investigate the functions of different LGI1 point mutations, including LGI1W183R, in regulating hippocampal neuronal excitability. Our research will promote the understanding of the pathogenesis of ADLTE and provide a theoretical basis for its therapeutic targets.