癫痫共病现象日益突出，其机制不明。5-羟色胺6 受体（5-HTR6）与认知关系密切，迄今5-HTR6与癫痫的关系知之甚少。其介导mTOR等信号通路与细胞凋亡、自噬、突触重塑密切相关，前期研究发现5-HTR6拮抗剂可增加癫痫大鼠KCNQ3表达、改善突触可塑性，因此我们推测5-HTR6介导mTOR调节M-电流及突触可塑性。为验证这一假说，本项在前期研究基础上，应用氯化铝-匹罗卡品慢性癫痫模型、培养海马神经元、收集TLE患者手术海马标本，通过病毒包装的shRNA敲低或过表达5-HTR6和mTOR，采用行为学、神经电生理、分子生物学等技术观察5-HTR6表达变化对痫性放电、认知情感、突触可塑性的影响，探讨5-HTR6在不同神经元中启动不同丢失方式（自噬/凋亡/坏死）的机制及介导mTOR调节M-电流及突触可塑性的机制。研究结果将为癫痫海马损伤机制提供新思路，为癫痫共病的防治提供新的药理靶点和机制。

The phenomenon of epileptic complication become more and more obvious. About 35% temporal lobe epileptic patients are accompanied by cognitive and mood impairment. But the mechanism remains unclear. One of the main reasons is hippocampal sclerosis. Recently, 5-HT6 receptor (5-HTR6) is considered to be related to cognition and epilepsy via such mTOR signaling. Interesting, 5-HT6 receptor antagonist SB-271046 was found to attenuate seizures and improve cognition in pilocarpine-induced chronic epileptic rats in our previous experiment. Increased expression of KCNQ3 mRNA and improvement of LTP after SB-271046 intervention was further observed in our rat model. So we suppose that 5-HTR6 modulates M-current and neuronal plasticity via such mTOR. To explore how 5-HTR6 to modulates M-current and neuronal plasticity. Based on our previous research, the chronic epileptic rats are induced by pilocarpine and hippocampal neurons are cultured. At the same time, the hippocampus of TLE patients are collected. Then the rats or the neurons are intervened by retroviruses packaged shRNA-5-HTR6/mTOR or their antagonists /agonists. The behavior (such as discharges, cognitive impairment, mood function, LTP/LTD) of rats or neurons are observed and the mechanisms of 5-HTR6 modulating M-current / neurons loss /neuronal plasticity are explored via neuro-electrophysiological and molecular-biological methods. This study would provide new insight into the mechanism of hippocampus sclerosis in epilepsy and provide new targets (such as 5-HTR6, mTOR) of preventing epileptic complication.