Kalium channelrhodopsins effectively inhibit neurons

Stanislav Ott, Sangyu Xu, Nicole Lee, Ivan Hong, Jonathan Anns, Danesha Devini Suresh, Zhiyi Zhang, Xianyuan Zhang, Raihanah Harion, Weiying Ye, Vaishnavi Chandramouli, Suresh Jesuthasan, Yasunori Saheki and Adam Claridge-Chang ()
Additional contact information
Stanislav Ott: Duke-NUS Medical School
Sangyu Xu: A*STAR Agency for Science, Technology and Research
Nicole Lee: Duke-NUS Medical School
Ivan Hong: Duke-NUS Medical School
Jonathan Anns: A*STAR Agency for Science, Technology and Research
Danesha Devini Suresh: Duke-NUS Medical School
Zhiyi Zhang: Duke-NUS Medical School
Xianyuan Zhang: Duke-NUS Medical School
Raihanah Harion: Nanyang Technological University
Weiying Ye: National University of Singapore
Vaishnavi Chandramouli: Nanyang Technological University
Suresh Jesuthasan: Nanyang Technological University
Yasunori Saheki: Nanyang Technological University
Adam Claridge-Chang: Duke-NUS Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-47203-w

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