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Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects.
Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Nature Communications, ISSN 2041-1723, EISSN 2041-1723, ISSN 2041-1723, Vol. 9, no 1, article id 219Article in journal (Refereed) Published
Abstract [en]

Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease. To determine whether drugs that enhance BAP complexity produces positive outcomes, we used light pulses to trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy. The highest-ranked compounds identified by BAP analysis exhibit far greater anti-seizure efficacy and fewer side effects during subsequent in-depth behavioral assessment. This high correlation with behavioral outcomes illustrates the power of brain activity pattern-based screens and identifies novel therapeutic candidates with minimal side effects.

Place, publisher, year, edition, pages
2018. Vol. 9, no 1, article id 219
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Neurosciences
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URN: urn:nbn:se:uu:diva-397347DOI: 10.1038/s41467-017-02404-4PubMedID: 29335539OAI: oai:DiVA.org:uu-397347DiVA, id: diva2:1371287
Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2020-01-15Bibliographically approved

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