eLife (Oct 2024)

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

  • Johannes Oppermann,
  • Andrey Rozenberg,
  • Thomaz Fabrin,
  • Cristian González-Cabrera,
  • Rafael Parker,
  • Oded Béjà,
  • Matthias Prigge,
  • Peter Hegemann

DOI
https://doi.org/10.7554/eLife.90100
Journal volume & issue
Vol. 12

Abstract

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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.

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