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Kalium channelrhodopsins effectively inhibit neurons.
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
Institute for Molecular and Cell Biology, A*STAR Agency for Science, Technology and Research, Singapore, Singapore.
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 3480Article in journal (Refereed) Published
Abstract [en]

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditis elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 15, no 1, article id 3480
National Category
Biological Sciences
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URN: urn:nbn:se:umu:diva-231214DOI: 10.1038/s41467-024-47203-wISI: 001217093700013PubMedID: 38658537Scopus ID: 2-s2.0-85191317138OAI: oai:DiVA.org:umu-231214DiVA, id: diva2:1929040
Available from: 2025-01-19 Created: 2025-01-19 Last updated: 2025-01-20Bibliographically approved

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Jesuthasan, Suresh

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