Glia-neuron interactions underlie state transitions to generalized seizures
Glia-neuron interactions underlie state transitions to generalized seizures
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DOI：
10.1038/s41467-019-11739-z
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发表时间：
2019-01
影响因子：
16.6
通讯作者：
Carmen Diaz Verdugo;Sverre Myren-Svelstad;Ecem Aydın;Evelien Van Hoeymissen;Celine Deneubourg;Silke Vanderha
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文献类型：
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作者：
Carmen Diaz Verdugo;Sverre Myren-Svelstad;Ecem Aydın;Evelien Van Hoeymissen;Celine Deneubourg;Silke Vanderha
癫痫发作期间大脑活动和连接性会发生巨大变化。大脑网络从平衡的休息状态转变为过度活跃和超同步状态。然而，尚不清楚哪些机制是状态转换的基础。通过研究斑马鱼癫痫发作模型中的神经和神经胶质活动，我们观察到这些网络之间的显着差异。在发作前期间，神经元仅在局部表现出同步活动的小幅增加，而间隙连接耦合的神经胶质网络在长距离内高度活跃且强烈同步。从发作前状态到全身性癫痫发作的转变会导致神经活动和连接性突然增加，同时伴随着神经胶质-神经元相互作用的强烈改变和细胞外谷氨酸的大量增加。神经胶质细胞的光遗传学激活通过谷氨酸和间隙连接的作用激发附近的神经元，强调神经胶质细胞-神经胶质细胞和神经胶质细胞-神经元连接在癫痫发作的产生中的潜在作用。
Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state. It is, however, less clear which mechanisms underlie the state transitions. By studying neural and glial activity in zebrafish models of epileptic seizures, we observe striking differences between these networks. During the preictal period, neurons display a small increase in synchronous activity only locally, while the gap-junction-coupled glial network was highly active and strongly synchronized across large distances. The transition from a preictal state to a generalized seizure leads to an abrupt increase in neural activity and connectivity, which is accompanied by a strong alteration in glia-neuron interactions and a massive increase in extracellular glutamate. Optogenetic activation of glia excites nearby neurons through the action of glutamate and gap junctions, emphasizing a potential role for glia-glia and glia-neuron connections in the generation of epileptic seizures.