齿状回生长抑素神经元介导微环路在皮质发育不良癫痫中的机制研究

局灶性皮质发育不良（FCD）I型相关癫痫普遍药物难治、手术效果不佳。研究认为广泛的脑网络改变是FCDI型预后不良的主要原因，而寻找癫痫网络的关键节点是目前亟待解决的关键科学问题之一。我们前期研究发现海马在FCDI型中具有较高致痫性；且海马齿状回生长抑素神经元相关微环路可能介导了FCDI型癫痫网络的传播与扩散。基于以上基础，本项目提出“齿状回生长抑素神经元相关微环路可能是FCDI型癫痫网络中关键节点”的科学假设。拟进一步利用功能磁共振及脑电分析等临床方法，结合钙信号记录、光遗传学调控、病毒荧光示踪剂追踪、离体电生理等实验手段揭示齿状回生长抑素阳性神经元相关微环路在FCDI型癫痫网络中的作用与特征，并阐明阳离子-氯离子共转运蛋白参与该微环路异常的具体机制。本项目成果将有助于解析皮质发育不良相关癫痫的环路机制，为FCDI型的精准治疗提供崭新视角。

Focal cortical dysplasia (FCD) type I is mostly drug-refractory, and responds poorly to surgery as well. Current research attributes its poor prognosis mainly to network changes at the macrocircuit level. Therefore, identification of the hub region within the epileptogenic network, which has the potential to affect the whole brain, is of utmost importance. Previously, we found that patients with FCD type I had a high epileptogenic index of the hippocampus. With rodent models of cortical dysplasia, we also identified somatostatin-positive-neuron-mediated microcircuit (SST-mediated microcircuit) in the dentate gyrus the main contributor to the epileptogenic network in FCD type I. Based on those results, we hypothesized SST-mediated microcircuit in the dentate gyrus to be the hub in the FCD type I network. Therefore, with multi-faceted approaches, both clinically and experimentally, this project is aimed to elucidate the features of SST-mediated microcircuit in FCD type I as well as the underlying mechanism. Hopefully, our project would provide a deeper understanding of the epileptogenesis of cortical dysplasia at the network level, and offer a new insight in the treatment of FCD type I.