Robust optogenetic inhibition with red-light-sensitive anion-conducting channelrhodopsins
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 ( λ max 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.
Authors
- Thomaz Mansini Carrenho Fabrin (ORCID: https://orcid.org/0000-0002-4529-7106)
- Johannes Oppermann (ORCID: https://orcid.org/0000-0002-3442-1458)
- Peter Hegemann (ORCID: https://orcid.org/0000-0003-3589-6452)
- Andrey Rozenberg (ORCID: https://orcid.org/0000-0001-9534-2297)
- Matthias Prigge (ORCID: https://orcid.org/0000-0002-4923-0056)
- Cristian González‐Cabrera (ORCID: https://orcid.org/0000-0003-0515-0254)
- Oded Béjà (ORCID: https://orcid.org/0000-0001-6629-0192)
- Rafael ES Parker (ORCID: https://orcid.org/0009-0000-0770-0438)
Institutions
- Technion – Israel Institute of Technology (IL)
- Humboldt-Universität zu Berlin (DE)
- Center for Behavioral Brain Sciences (DE)
- Research Network (United States) (US)
- Leibniz Institute for Neurobiology (DE)
Publication Details
- Journal
- eLife
- Published
- 2024-10-14
- DOI
- https://doi.org/10.7554/elife.90100.3
- Citations
- 1
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.27
Funders
- Alexander von Humboldt-Stiftung
- EU Joint Programme – Neurodegenerative Disease Research
- Deutsche Forschungsgemeinschaft
- Israel Science Foundation