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Evolution of Epileptiform Activity in Zebrafish by Statistical-Based Integration of Electrophysiology and 2-Photon Ca2+ Imaging

1
National Enterprise for Nanoscience and Nanotechnology (NEST), Istituto Nanoscienze Consiglio Nazionale delle Ricerche (CNR) and Scuola Normale Superiore Pisa, 56127 Pisa, Italy
2
Molecular Medicine, IRCCS Fondazione Stella Maris, Via dei Giacinti 2, 56028 Pisa, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(3), 769; https://doi.org/10.3390/cells9030769
Received: 16 February 2020 / Revised: 14 March 2020 / Accepted: 18 March 2020 / Published: 21 March 2020
(This article belongs to the Special Issue Signaling Pathway Analysis and Disease Modeling in Zebrafish)
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 Ca2+ imaging. We developed a method to extract and quantify electrophysiological transients coupled with Ca2+ 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. View Full-Text
Keywords: epilepsy; zebrafish; statistical-based analysis; two-photon calcium imaging; electrophysiology epilepsy; zebrafish; statistical-based analysis; two-photon calcium imaging; electrophysiology
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Cozzolino, O.; Sicca, F.; Paoli, E.; Trovato, F.; Santorelli, F.M.; Ratto, G.M.; Marchese, M. Evolution of Epileptiform Activity in Zebrafish by Statistical-Based Integration of Electrophysiology and 2-Photon Ca2+ Imaging. Cells 2020, 9, 769.

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