Robust optogenetic inhibition with red-light-sensitive anion-conducting channelrhodopsins.

Oppermann, Johannes; Rozenberg, Andrey; Fabrin, Thomaz; González-Cabrera, Cristian; Parker, Rafael; Béjà, Oded; Prigge, Matthias; Hegemann, Peter · Elife · 2024

basic_science · Level V

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Abstract

Channelrhodopsins (ChRs) are light-gated ion channels widely used to optically activate or silence selected electrogenic cells, such as individual brain neurons. Here, we describe identifying and characterizing a set of anion-conducting ChRs (ACRs) from diverse taxa and representing various branches of the ChR phylogenetic tree. The <i>Mantoniella squamata</i> ACR (MsACR1) showed high sensitivity to yellow-green light (<i>λ</i><sub>max</sub> at 555 nm) and was further engineered for optogenetic applications. A single amino-acid substitution that mimicked red-light-sensitive rhodopsins like Chrimson shifted the photosensitivity 20 nm toward red light and accelerated photocurrent kinetics. Hence, it was named red and accelerated ACR, raACR. Both wild-type and mutant are capable optical silencers at low light intensities in mouse neurons <i>in vitro</i> and <i>in vivo</i>, while raACR offers a higher temporal resolution.

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