光遗传学
沟道视紫红质
斑马鱼
钾通道
细胞生物学
化学
氯化物
秀丽隐杆线虫
钾
生物
生物物理学
药理学
神经科学
生物化学
基因
有机化学
作者
Stanislav Ott,Sangyu Xu,Nicole Lee,Ivan Hee Kean Hong,Jonathan Anns,Danesha Devini Suresh,Z Zhang,Xianyuan Zhang,Raihanah Harion,Weiying Vivian Ye,Vaishnavi Chandramouli,Suresh Jesuthasan,Yasunori Saheki,Adam Claridge‐Chang
标识
DOI:10.1038/s41467-024-47203-w
摘要
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.
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