Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, Magdeburg, Germany; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States
Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, Magdeburg, Germany; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States
Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, Magdeburg, Germany; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States; Center for Behavioral Brain Sciences, CBBS, Magdeburg, Germany
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 Mantoniella squamata ACR (MsACR1) showed high sensitivity to yellow-green light (λmax 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 in vitro and in vivo, while raACR offers a higher temporal resolution.