Optical mapping of neuronal activity during seizures in zebrafish

Year: 2017

Authors: Turrini L., Fornetto C., Marchetto G., Müllenbroich M.C., Tiso N., Vettori A., Resta F., Masi A., Mannaioni G., Pavone F.S., Vanzi F.

Autors Affiliation: European Lab Nonlinear Spect LENS, Sesto Fiorentino, Italy; Univ Florence, Dept Biol, Sesto Fiorentino, Italy; Natl Res Council CNR, Natl Inst Opt INO, Sesto Fiorentino, Italy; Univ Padua, Dept Biol, Padua, Italy; Univ Florence, Dept Neurofarba, Florence, Italy; Univ Florence, Dept Phys, Sesto Fiorentino, Italy.

Abstract: Mapping neuronal activity during the onset and propagation of epileptic seizures can provide a better understanding of the mechanisms underlying this pathology and improve our approaches to the development of new drugs. Recently, zebrafish has become an important model for studying epilepsy both in basic research and in drug discovery. Here, we employed a transgenic line with pan-neuronal expression of the genetically-encoded calcium indicator GCaMP6s to measure neuronal activity in zebrafish larvae during seizures induced by pentylenetretrazole (PTZ). With this approach, we mapped neuronal activity in different areas of the larval brain, demonstrating the high sensitivity of this method to different levels of alteration, as induced by increasing PTZ concentrations, and the rescuing effect of an anti-epileptic drug. We also present simultaneous measurements of brain and locomotor activity, as well as a high-throughput assay, demonstrating that GCaMP measurements can complement behavioural assays for the detection of subclinical epileptic seizures, thus enabling future investigations on human hypomorphic mutations and more effective drug screening methods. Notably, the methodology described here can be easily applied to the study of many human neuropathologies modelled in zebrafish, allowing a simple and yet detailed investigation of brain activity alterations associated with the pathological phenotype.

Journal/Review: SCIENTIFIC REPORTS

Volume: 7      Pages from: 3025-1  to: 3025-12

More Information: We thank Dr. Leonardo Sacconi for discussions, Mr. Riccardo Ballerini for technical assistance, and Dr. Misha Ahrens for gift of the Tol2-elavl3-GCaMP6s plasmid. This work was supported by grants from Ente Cassa di Risparmio di Firenze (private foundation), Italian Flagship NanoMax, Ministero della Salute (Ricerca Finalizzata grant number GR-2011-02346749), Eurobioimaging – Advanced Light Microscopy Italian Node, AFM Telethon project POLYGON (18572), and the European Union´s Horizon 2020 research and innovation programme under grant agreement No 654148 Laserlab-Europe.
KeyWords: Animals; Biomarkers; Brain; Calcium; Disease Models, Animal; High-Throughput Screening Assays; Molecular Imaging; Muscle Contraction; Neurons; Optical Imaging; Pentylenetetrazole; Seizures; Zebrafish; Mind-bomb; Epilepsy; Expressiom; Behavior; Drugs
DOI: 10.1038/s41598-017-03087-z

Citations: 67
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