Neuronal hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission, but the synaptic alterations leading to enhanced seizure propensity are only partly understood. Taking advantage of a mouse model of neocortical epilepsy, we used a combination of photoconversion and electron microscopy to assess changes in synaptic vesicles pools in vivo. Our analyses reveal that epileptic networks show an early onset lengthening of active zones at inhibitory synapses, together with a delayed spatial reorganization of recycled vesicles at excitatory synapses. Proteomics of synaptic content indicate that specific proteins were increased in epileptic mice. Altogether, our data reveal a complex landscape of nanoscale changes affecting the epileptic synaptic release machinery. In particular, our findings show that an altered positioning of release-competent vesicles represent a novel signature of epileptic networks.

神经元过度兴奋通常是由兴奋性和抑制性神经传递之间的不平衡引起的，但是导致癫痫发作倾向增强的突触改变只是部分被理解。利用新皮质癫痫的小鼠模型，我们结合使用了光转换和电子显微镜来评估突触囊泡池的变化体内。我们的分析表明，癫痫网络显示抑制性突触中活性区的早期发作延长，以及兴奋性突触中再生囊泡的空间重组延迟。突触内容的蛋白质组学表明，癫痫小鼠中的特定蛋白质增加了。总之，我们的数据揭示了影响癫痫突触释放机制的纳米级变化的复杂情况。特别地，我们的发现表明，具有释放能力的囊泡的位置改变代表了癫痫网络的新特征。