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.

Multimodal Characterization of Seizures in Zebrafish Larvae / Lapo Turrini , Michele Sorelli, Giuseppe de Vito , Caterina Credi , Natascia Tiso , Francesco Vanzi , Francesco Saverio Pavone. - In: BIOMEDICINES. - ISSN 2227-9059. - ELETTRONICO. - 10:(2022), pp. 951-951. [10.3390/biomedicines10050951]

Multimodal Characterization of Seizures in Zebrafish Larvae

Lapo Turrini
;
Michele Sorelli;Giuseppe de Vito;Francesco Vanzi;Francesco Saverio Pavone
2022

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.
2022
10
951
951
Lapo Turrini , Michele Sorelli, Giuseppe de Vito , Caterina Credi , Natascia Tiso , Francesco Vanzi , Francesco Saverio Pavone
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1265097
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