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Robust optogenetic inhibition with red-light-sensitive anion-conducting channelrhodopsins
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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 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.
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Metadata
- Authors
- Oppermann, J., Rozenberg, A., Fabrin, T., González-Cabrera, C., Parker, R., Béjà, O., Prigge, M., & Hegemann, P.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Technion – Israel Institute of Technology (IL)
- Leibniz Institute for Neurobiology (DE)
- Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology
- Corresponding author
- Oppermann, Johannes
- Prigge, Matthias
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2024-10-14
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4380153716
- Cited by
- 2
- References
- 2
- Citations by year
- 2025: 2
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PUBLISSO (German National Library of Medicine) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 1078 B2 221545957)
- Israel Science Foundation (3131/20)
- Alexander von Humboldt-Stiftung (99999.001756/2014-01)
- EU Joint Programme – Neurodegenerative Disease Research (JPco-FuND - NiPARK)
- Leibniz-Gemeinschaft (Program 'BestMinds' MP J28/2017 SheLi)
- Aligning Science Across Parkinson’s (ASAP-020505)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- channelrhodopsin, optogenetic inhibition, red light sensitivity, photocurrent kinetics, neuronal silencing, light-gated ion channels
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