Department of Neurological Surgery and Weill Institute for Neuroscience, University of California, San Francisco, CA 94143.
eNeuro. 2019 Mar 11;6(1). doi: 10.1523/ENEURO.0041-19.2019. eCollection 2019 Jan-Feb.
Seizures are characterized by hypersynchronization of neuronal networks. Understanding these networks could provide a critical window for therapeutic control of recurrent seizure activity, i.e., epilepsy. However, imaging seizure networks has largely been limited to microcircuits or small "windows" . Here, we combine fast confocal imaging of genetically encoded calcium indicator (GCaMP)-expressing larval zebrafish with local field potential (LFP) recordings to study epileptiform events at whole-brain and single-neuron levels . Using an acute seizure model (pentylenetetrazole, PTZ), we reliably observed recurrent electrographic ictal-like events associated with generalized activation of all major brain regions and uncovered a well-preserved anterior-to-posterior seizure propagation pattern. We also examined brain-wide network synchronization and spatiotemporal patterns of neuronal activity in the optic tectum microcircuit. Brain-wide and single-neuronal level analysis of PTZ-exposed and 4-aminopyridine (4-AP)-exposed zebrafish revealed distinct network dynamics associated with seizure and non-seizure hyperexcitable states, respectively. Neuronal ensembles, comprised of coactive neurons, were also uncovered during interictal-like periods. Taken together, these results demonstrate that macro- and micro-network calcium motifs in zebrafish may provide a greater understanding of epilepsy.
癫痫发作的特征是神经元网络的超同步化。理解这些网络可以为治疗复发性癫痫活动（即癫痫）提供一个关键窗口。然而，对癫痫发作网络的成像在很大程度上仅限于微电路或小的“窗口”。在这里，我们将遗传编码钙指示剂（GCaMP）表达的幼虫斑马鱼的快速共焦成像与局部场电位（LFP）记录相结合，以在全脑和单个神经元水平上研究癫痫样事件。使用急性癫痫发作模型（戊四氮，PTZ），我们可靠地观察到与所有主要脑区广泛激活相关的复发性电发作样事件，并揭示了一种保存完好的从前到后的癫痫发作传播模式。我们还检查了光顶盖微电路中的脑广泛网络同步和神经元活动的时空模式。对暴露于 PTZ 和 4-氨基吡啶（4-AP）的斑马鱼进行全脑和单个神经元水平的分析显示，与癫痫发作和非癫痫发作高兴奋性状态相关的网络动力学明显不同。在类似发作间期也发现了由共同活跃神经元组成的神经元集合。总之，这些结果表明，斑马鱼的宏观和微观网络钙基序可能为理解癫痫提供了更多的认识。
