High-throughput Analysis of Synaptic Activity in Electrically Stimulated Neuronal Cultures.

Autor: Van Dyck M; Laboratory of Cell Biology and Histology, University of Antwerp, CDE, Antwerp, Belgium.; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Mishra RK; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium.; iOligos Technologies Private Limited, 1703, CB2, Supertech Capetown, Sector-74, 201301, Noida, India., Pestana F; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Verstraelen P; Laboratory of Cell Biology and Histology, University of Antwerp, CDE, Antwerp, Belgium., Lavreysen H; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Pita-Almenar JD; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Kashikar ND; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium. nachiket.kashikar@resolve-biosciences.com.; Resolve BioSciences GmbH, Creative Campus Monheim Gebäude A03, Alfred-Nobel-Strasse 10, 40789, Monheim am Rhein, Germany. nachiket.kashikar@resolve-biosciences.com., De Vos WH; Laboratory of Cell Biology and Histology, University of Antwerp, CDE, Antwerp, Belgium. Winnok.DeVos@uantwerpen.be.
Jazyk: angličtina
Zdroj: Neuroinformatics [Neuroinformatics] 2021 Oct; Vol. 19 (4), pp. 737-750. Date of Electronic Publication: 2021 Aug 10.
DOI: 10.1007/s12021-021-09536-5
Abstrakt: Synaptic dysfunction is a hallmark of various neurodegenerative and neurodevelopmental disorders. To interrogate synapse function in a systematic manner, we have established an automated high-throughput imaging pipeline based on fluorescence microscopy acquisition and image analysis of electrically stimulated synaptic transmission in neuronal cultures. Identification and measurement of synaptic signal fluctuations is achieved by means of an image analysis algorithm based on singular value decomposition. By exploiting the synchronicity of the evoked responses, the algorithm allows disentangling distinct temporally correlated patterns of firing synapse populations or cell types that are present in the same recording. We demonstrate the performance of the analysis with a pilot compound screen and show that the multiparametric readout allows classifying treatments by their spatiotemporal fingerprint. The image analysis and visualization software has been made publicly available on Github ( https://www.github.com/S3Toolbox ). The streamlined automation of multi-well image acquisition, electrical stimulation, analysis, and meta-data warehousing facilitates large-scale synapse-oriented screens and, in doing so, it will accelerate the drug discovery process.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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