National Enterprise for Nanoscience and Nanotechnology (NEST), Istituto Nanoscienze Consiglio Nazionale delle Ricerche (CNR) and Scuola Normale Superiore Pisa, 56127 Pisa, Italy.
Molecular Medicine, IRCCS Fondazione Stella Maris, Via dei Giacinti 2, 56028 Pisa, Italy.
Cells. 2020 Mar 21;9(3):769. doi: 10.3390/cells9030769.
The study of sources and spatiotemporal evolution of ictal bursts is critical for the mechanistic understanding of epilepsy and for the validation of anti-epileptic drugs. Zebrafish is a powerful vertebrate model representing an excellent compromise between system complexity and experimental accessibility. We performed the quantitative evaluation of the spatial recruitment of neuronal populations during physiological and pathological activity by combining local field potential (LFP) recordings with simultaneous 2-photon Ca imaging. We developed a method to extract and quantify electrophysiological transients coupled with Ca events and we applied this tool to analyze two different epilepsy models and to assess the efficacy of the anti-epileptic drug valproate. Finally, by cross correlating the imaging data with the LFP, we demonstrated that the cerebellum is the main source of epileptiform transients. We have also shown that each transient was preceded by the activation of a sparse subset of neurons mostly located in the optic tectum.
研究癫痫发作的起源和时空演变对于深入理解癫痫机制和验证抗癫痫药物至关重要。斑马鱼是一种强大的脊椎动物模型，在系统复杂性和实验可及性之间达到了很好的平衡。我们通过将局部场电位 (LFP) 记录与同时进行的双光子 Ca2+成像相结合，对生理和病理活动期间神经元群体的空间募集进行了定量评估。我们开发了一种提取和量化与 Ca2+事件相关的电生理瞬变的方法，并应用该工具分析了两种不同的癫痫模型，评估了抗癫痫药物丙戊酸钠的疗效。最后，通过将成像数据与 LFP 进行交叉相关，我们证明了小脑是癫痫样瞬变的主要起源。我们还表明，每个瞬变之前都伴随着一小部分神经元的激活，这些神经元主要位于视顶盖中。
