颞叶癫痫是成年人一种最常见的癫痫形式，但是关于它的分子机制仍然知之甚少。海人酸受体在癫痫发生中发挥重要的作用，尤其亚单位GluR6近期受到人们的关注。巯基亚硝基化作为蛋白质翻译后修饰的一种形式广泛影响细胞功能。然而并不清楚GluR6巯基亚硝基化在癫痫发生中的作用，以及胞内钙离子如何调节GluR6巯基亚硝基化。本项目首先在体外培养的海马神经元和体内海人酸诱导的动物癫痫模型上探讨内源性和外源性一氧化氮以及不同路径的钙离子流如何影响海马内GluR6巯基亚硝基化、GluR6介导的全细胞电流以及癫痫行为和海马损伤。继而采用遗传学位点突变方法进一步明确GluR6巯基亚硝基化在癫痫行为和海马损伤中作用。最后在不同病理类型和不同病程的颞叶癫痫患者上确定不同海马区GluR6亚单位的表达和巯基亚硝基化水平以及它与癫痫的相关性。总之，该项目不仅加深理解癫痫的发生机制，而且为研发抗癫痫药物提供新的靶点。

Temporal lobe epilepsy (TLE) is the most common form of adults. Despite intensive research, the molecular mechanisms for TLE remains poorly understood. Kainate receptors, as a kind of ionotropic glutamate receptors, play an important role in epileptogenesis. Recently, its subunit GluR6 attracts great attention. S-nitrosylation, as an important form of protein post-translational modification, widely affects cell functions. However, it is unclear whether S-nitrosylation of GluR6 itself is involved in epileptogenesis, as well as how the level of intracellular calcium regulates S-nitrosylation of GluR6. By using in vitro cultured hippocampal neurons, Kainic acid-induced epileptic animal model, the proposal will focus on how endogenous/exogenous nitric oxide and different routes of calcium ion flow affects S-nitrosylation of GluR6 in the hippocampus neurons, GluR6-mediated whole cell current, as well as epilepsy behavior and hippocampal damage. Subsequently, the proposal will determine the role of S-nitrosylation of GluR6 in epilepsy behavior and hippocampal damage by using genetic site mutation. Finally, the proposal will examine the expression level and S-nitrosylation of GluR6 in different regions of the hippocampus of TLE patients with different pathological types and different duration of disease, and then evaluate its correlations with epilepsy. Taken together, the proposal will not only deepen the understanding of pathogenesis of epilepsy, but also provide a new target for epilepsy and other relevant neurological diseases.