成年小鼠癫痫发作早期突触内、外N-甲基-D-天冬氨酸受体介导的电流变化

在癫痫疾病的发生和反复发作的过程中，N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体（NMDA受体）起着重要的作用。近年来的研究发现，突触内和突触外的NMDA受体在包括突触可塑性和细胞死亡的信号通路中起着不同的甚至是截然相反的作用。因此，我们在本研究中探讨了突触内、外NMDA受体介导的兴奋性突触后电流在癫痫发病的病理过程中的变化。我们利用氯化锂联合匹罗卡品（pilocarpine, PILO）诱导了成年癫痫小鼠模型，并在癫痫发作24小时后制作了急性海马切片，利用膜片钳全细胞记录法对CA1区锥体神经元的突触内、外NMDA受体电流进行了记录。我们发现，1）突触内NMDA受体电流的上升时间及衰减时间与对照组比较均无统计学差异；2）突触外NMDA受体电流的兴奋性电流峰值、面积峰值比、以及上升时间亦无统计学差异；3）但突触外电流的衰减时程相对于对照组加快。以上结果提示突触外NMDA受体可能参与癫痫的发病机制。

Changes in synaptic and extrasynaptic N-methyl-D-aspartate receptor-mediated currents at early-stage epileptogenesis in adult mice

Previous reports have shown that N-methyl-D-aspartate (NMDA) receptors are extensively involved in epilepsy genesis and recurrence. Recent studies have shown that synaptic and extrasynaptic NMDA receptors play different, or even opposing, roles in various signaling pathways, including synaptic plasticity and neuronal death. The present study analyzed changes in synaptic and extrasynaptic NMDA receptor-mediated currents during epilepsy onset. Mouse models of lithium chloride pilocarpine-induced epilepsy were established, and hippocampal slices were prepared at 24 hours after the onset of status epilepticus. Synaptic and extrasynaptic NMDA receptor-mediated excitatory post-synaptic currents (NMDA-EPSCs) were recorded in CA1 pyramidal neurons by whole-cell patch clamp technique. Results demonstrated no significant difference in rise and delay time of synaptic NMDA-EPSCs compared with normal neurons. Peak amplitude, area-to-peak ratio, and rising time of extrasynaptic NMDA-EPSCs remained unchanged, but decay of extrasynaptic NMDA-EPSCs was faster than that of normal neurons. These results suggest that extrasynaptic NMDA receptors play a role in epileptogenesis.