颞叶癫痫是一种高发的难治性脑病，主要特征是神经元超级兴奋及超级同步发放，伴有海马齿状回HIPP神经元大量死亡。关于神经元间电突触如何调控癫痫神经网络的兴奋性和同步性已有大量研究，但电突触是否以及如何调控癫痫过程中HIPP神经元特异性死亡仍是未知。最近体外实验发现电突触在谷氨酸诱导神经元死亡中起关键作用,我们前期研究证明海马齿状回中各种同类中间神经元间均有电突触，同时癫痫发作后大量存活的中间神经元类型间电突触联系明显降低。因此我们认为：首次癫痫发生后，电突触特异在HIPP神经元上大量表达，从而促进了HIPP神经元大量死亡。本项目将运用膜片钳配对记录和单细胞RT-PCR研究癫痫发生过程中海马齿状回中各类中间神经元电突触及其调控因子变化，同时利用体外脑片培养和在体实验探索电突触介导HIPP神经元特异性死亡的具体机制。本项目将有助于我们进一步了解癫痫的发生机制，从而为癫痫的治疗提供新的思路和靶标。

Temporal lobe epilepsy is one common refractory disease which is characterized with hyper excitability and hyper synchrony among brain neurons, accompanied with abundant cell death of HIPP interneurons in hippocampal dentate gyrus. Although there are various studies reporting the regulation of excitability and synchronization between neurons by electrical synapses in epilepsy, whether electrical synapses are involved in HIPP cell specific death during epilepsy is not known. Recently it was found that electrical synapses played a key role in glutamate-dependent neural death, and our preliminary experiments demonstrated that (1) dentate gyrus interneurons have electrical synapses expression, and (2) the probability of electrical synaptic connection among surviving interneurons after epilepsy is significantly decreased. Therefore, we made the hypothesis: electrical synapses between HIPP interneurons are up-regulated after epilepsy, further causing HIPP neuronal death. This project will use paired whole-cell recordings to study the functional changes of electrical synapses and single cell RT-PCR for their gene expression in dentate gyrus interneurons after status epilepticus. We will also use in vitro hippocampal slice organotypic culture and in vivo model to study mechanisms of electrical synapses mediating HIPP specific death after epilepsy. This study will benefit the characterization of dentate electrical synapses network in epilepsy, thus enriching our knowledge of epilepsy pathogenesis and providing novel targets and strategies in clinical treatment.