Network Properties Revealed During Multi-Scale Calcium Imaging of Seizure Activity in Zebrafish Liu J, Baraban SC. eNeuro. 2019;6(1):ENEURO.0041-19.2019. doi:10.1523/ENEURO.0041-19.2019. eCollection 2019 Jan-Feb. PMID: 30895220. Seizures are characterized by hypersynchronization of neuronal networks. Understanding these networks could provide a critical window for therapeutic control of recurrent seizure activity, that is, epilepsy. However, imaging seizure networks have largely been limited to microcircuits in vitro or small "windows" in vivo. Here, we combine fast confocal imaging of genetically encoded calcium indicator-expressing larval zebrafish with local field potential recordings to study epileptiform events at whole-brain and single-neuron levels in vivo. 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-exposed zebrafish revealed distinct network dynamics associated with seizure and nonseizure 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.

中文翻译：

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在斑马鱼癫痫发作活动的多尺度钙成像中揭示的网络特性 Liu J，Baraban SC。电子神经。2019;6(1):ENEURO.0041-19.2019。doi:10.1523/ENEURO.0041-19.2019。eCollection 2019 年 1 月至 2 月 PMID：30895220。癫痫发作的特点是神经元网络的超同步。了解这些网络可以为治疗控制复发性癫痫活动（即癫痫）提供一个关键窗口。然而，成像癫痫网络在很大程度上仅限于体外微电路或体内小“窗口”。在这里，我们将表达基因编码钙指示剂的斑马鱼幼虫的快速共聚焦成像与局部场电位记录相结合，以研究体内全脑和单神经元水平的癫痫样事件。使用急性癫痫模型（戊四唑，PTZ），我们可靠地观察到与所有主要大脑区域的普遍激活相关的复发性电图发作样事件，并发现了保存完好的前后癫痫发作传播模式。我们还检查了全脑网络同步和视顶盖微电路中神经元活动的时空模式。PTZ 暴露和 4-氨基吡啶暴露斑马鱼的全脑和单神经元水平分析分别揭示了与癫痫发作和非癫痫发作过度兴奋状态相关的不同网络动态。在间歇期期间也发现了由协同神经元组成的神经元集合。总之，这些结果表明斑马鱼中的宏观和微观网络钙基序可以提供对癫痫的更好理解。