癫痫猝死（SUDEP）是神经科急危重症，其发病机制不明，缺乏确切的预防手段。最新研究发现，选择性5-羟色胺（5-HT）再摄取抑制剂可显著降低SUDEP模型动物呼吸骤停及部分性发作癫痫患者呼吸抑制的发生率，提示5-HT缺陷很可能是导致SUDEP的重要原因。中枢5-HT神经元位于脑内中缝核，参与觉醒、呼吸调控等生理功能，可能通过介导痫性发作相关性高碳酸血症对觉醒及呼吸中枢的影响参与SUDEP的发生。传统神经调控技术在实时调控特定核团特殊类型神经元活动上有明显的局限性，因此本项目拟采用新兴的光基因技术，通过慢病毒转染使光敏感离子通道ChR2选择性表达于DBA/1小鼠中缝核5-HT神经元，在此基础上建立SUDEP模型，利用蓝光激活ChR2通道特异性兴奋核团内5-HT神经元，以期通过上调脑内5-HT水平预防SUDEP的发生，为阐明SUDEP的发病机制、寻求预防SUDEP的潜在药物靶点提供实验依据。

Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event among neurological diseases, with unknown pathogenesis and uncertain preventive measures. Recent studies have shown that selective serotonin (5-, 5-hydroxytryptamine, 5-HT) reuptake inhibitor can significantly reduce the occurrence of respiratory inhibition observed in the SUDEP model and patients with partial epilepsy, suggesting that 5-HT deficiency may be an important cause of SUDEP. Central 5-HT neurons locate in the raphe nuclei in the pontine and medulla, exerting multiple physiological functions such as arousal and breathing regulation, therefore may involve in SUDEP via mediating arousal and respiratory reactions to seizure related hypercapnia. Traditional neuromodulation technologies have obvious limitations in cell-type specificity and temporal-spatial selectivity. Therefore, our projects aims to exert optogenetic technology in SUDEP model DBA/1 mice whose central 5-HT neurons in raphe nuclei selectively express light sensitive ion channel Channelrhodopsin-2 (ChR2) by gene transfection mediated by lentivirus. Then the central 5-HT neurons in raphe nuclei could be temporally activated by blue light to elevate the 5-HT level, aiming to prevent SUDEP, therefore to explore the pathogenesis of SUDEP, and to provide the potential preventive drug targets for SUDEP.