Bright and sensitive red voltage indicators for imaging action potentials in brain slices and pancreatic islets
Open accessPublished version of a preprint
Abstract
Genetically encoded voltage indicators (GEVIs) allow the direct visualization of cellular membrane potential at the millisecond time scale. Among these, red-emitting GEVIs have been reported to support multichannel recordings and manipulation of cellular activities with reduced autofluorescence background. However, the limited sensitivity and dimness of existing red GEVIs have restricted their applications in neuroscience. Here, we report a pair of red-shifted opsin-based GEVIs, Cepheid1b and Cepheid1s, with improved dynamic range, brightness, and photostability. The improved dynamic range is achieved by a rational design to raise the electrochromic Förster resonance energy transfer efficiency, and the higher brightness and photostability are approached with separately engineered red fluorescent proteins. With Cepheid1 indicators, we recorded complex firings and subthreshold activities of neurons on acute brain slices and observed heterogeneity in the voltage‑calcium coupling on pancreatic islets. Overall, Cepheid1 indicators provide a strong tool to investigate excitable cells in various sophisticated biological systems.
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- Authors
- Han, Y., Yang, J., Li, Y., Chen, Y., Ren, H., Ding, R., Qian, W., Ren, K., Xie, B., Deng, M., Xiao, Y., Chu, J., & Zou, P.
- Affiliations
- Peking University (CN)
- Nantong University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Yang, Junqi
- Zou, Peng
- ORCID
- Venue
- Science Advances
- Published
- 2023-11-24
- Volume
- 9
- Issue
- 47
- Pages
- eadi4208-eadi4208
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC10664999
- OpenAlex
- W4388901955
- Cited by
- 21
- References
- 7
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 2
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Harvard University
- National Natural Science Foundation of China (2017YFA0503600, 2018YFA0507600, 32 088 101, 21727806)
- Peking University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- 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
- Keywords
- genetically encoded voltage indicators, membrane potential, fluorescence resonance energy transfer, electrochromic shift, red fluorescent protein, photostability, dynamic range, brain slices, pancreatic islets, neuronal firing, subthreshold activity
- MeSH terms
- Action Potentials, Brain, Islets of Langerhans, Neurons, Fluorescence Resonance Energy Transfer
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