Multimodal Characterization of Seizures in Zebrafish Larvae

Year: 2022

Authors: Turrini L., Sorelli M., de Vito G., Credi C., Tiso N., Vanzi F., Pavone FS.

Autors Affiliation: Univ Florence, Dept Phys & Astron, Via G Sansone 1, I-50019 Sesto Fiorentino, Italy; European Lab Non Linear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Viale Pieraccini 6, I-50139 Florence, Italy; CNR, Natl Inst Opt, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Univ Padua, Dept Biol, Via Bassi 58 B, I-35131 Padua, Italy; Univ Florence, Dept Biol, Via Madonna Piano 6, I-50019 Sesto Fiorentino, Italy.

Abstract: Epilepsy accounts for a significant proportion of the world’s disease burden. Indeed, many research efforts are produced both to investigate the basic mechanism ruling its genesis and to find more effective therapies. In this framework, the use of zebrafish larvae, owing to their peculiar features, offers a great opportunity. Here, we employ transgenic zebrafish larvae expressing GCaMP6s in all neurons to characterize functional alterations occurring during seizures induced by pentylenetetrazole. Using a custom two-photon light-sheet microscope, we perform fast volumetric functional imaging of the entire larval brain, investigating how different brain regions contribute to seizure onset and propagation. Moreover, employing a custom behavioral tracking system, we outline the progressive alteration of larval swim kinematics, resulting from different grades of seizures. Collectively, our results show that the epileptic larval brain undergoes transitions between diverse neuronal activity regimes. Moreover, we observe that different brain regions are progressively recruited into the generation of seizures of diverse severity. We demonstrate that midbrain regions exhibit highest susceptibility to the convulsant effects and that, during periods preceding abrupt hypersynchronous paroxysmal activity, they show a consistent increase in functional connectivity. These aspects, coupled with the hub-like role that these regions exert, represent important cues in their identification as epileptogenic hubs.

Journal/Review: BIOMEDICINES

Volume: 10 (5)      Pages from: 951-1  to: 951-16

More Information: This research was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation program (grants agreement n.692943 and n.966623). This research has also been supported by the Italian Ministry for Education, University, and Research in the framework of the Advanced Lightsheet Microscopy Italian Node of Euro-Bioimaging ERIC, and by Bank Foundation Fondazione Cassa di Risparmio di Firenze with grants Human Brain Optical Mapping and 2020.1666.
KeyWords: epilepsy; seizure; zebrafish; calcium imaging; two-photon; light-sheet microscopy; behavior; tracking; functional connectivity
DOI: 10.3390/biomedicines10050951

ImpactFactor: 4.700
Citations: 7
data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-11-03
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