Efficient and sustained optogenetic control of sensory and cardiac systems

Alexey Alekseev; Victoria Hunniford; Maria Zerche; Marcus Jeschke; Fadhel El May; Anna Vavakou; Dominique Siegenthaler; Marc A. Hueser; Svenja M. Kiehn; Aida Garrido-Charles; Alexander Meyer; Adrian Rambousky; Theocharis Alvanos; Isabel Witzke; Keila Dara Rojas-Garcia; Martin D. Draband; Lukas Cyganek; Eric Klein; Patrick Ruther; Antoine Huet; Stuart Trenholm; Emilie Mace; Kathrin Kusch; Tobias Bruegmann; Bettina J. Wolf; Thomas Mager; Tobias Moser

doi:10.1038/s41551-025-01461-1

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Efficient and sustained optogenetic control of sensory and cardiac systems

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Efficient and sustained optogenetic control of sensory and cardiac systems

Alexey Alekseev, Victoria Hunniford, Maria Zerche, Marcus Jeschke, Fadhel El May, Anna Vavakou, Dominique Siegenthaler, Marc A. Hueser, Svenja M. Kiehn, Aida Garrido-Charles, …

Nature biomedical engineering

28/07/2025

DOI: https://doi.org/10.1038/s41551-025-01461-1

PMID: 40721511

Résumé

Engineering

Engineering, Biomedical

Science & Technology

Technology

Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.

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Détails

Titre: Efficient and sustained optogenetic control of sensory and cardiac systems
Créateurs - sans rôle: Alexey Alekseev - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Victoria Hunniford - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Maria Zerche - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Marcus Jeschke - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Fadhel El May - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Anna Vavakou - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Dominique Siegenthaler - Univ Gottingen, Cluster Excellence Multiscale Bioimaging Mol Mach, Gottingen, Germany
Marc A. Hueser - Univ Med Ctr Gottingen, Dept Otolaryngol, Gottingen, Germany
Svenja M. Kiehn - Univ Med Ctr Gottingen, Inst Cardiovasc Physiol, Gottingen, Germany
Aida Garrido-Charles - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Alexander Meyer - Univ Med Ctr Gottingen, Dept Otolaryngol, Gottingen, Germany
Adrian Rambousky - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Theocharis Alvanos - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Isabel Witzke - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Keila Dara Rojas-Garcia - McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
Martin D. Draband - Univ Med Ctr Gottingen, Inst Cardiovasc Physiol, Gottingen, Germany
Lukas Cyganek - Univ Med Ctr Gottingen, InnerEarLab, Gottingen, Germany
Eric Klein - Univ Freiburg, Dept Microsyst Engn IMTEK, Freiburg, Germany
Patrick Ruther - Univ Freiburg, Dept Microsyst Engn IMTEK, Freiburg, Germany
Antoine Huet - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Stuart Trenholm - McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
Emilie Mace - Univ Gottingen, Cluster Excellence Multiscale Bioimaging Mol Mach, Gottingen, Germany
Kathrin Kusch - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Tobias Bruegmann - Univ Gottingen, Cluster Excellence Multiscale Bioimaging Mol Mach, Gottingen, Germany
Bettina J. Wolf - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Thomas Mager - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Tobias Moser - Univ Med Ctr Gottingen, Inst Auditory Neurosci, Gottingen, Germany
Détails de publication: Nature biomedical engineering
Éditeur: NATURE PORTFOLIO
Nombre de pages: 31
Note de subvention: Max Planck Society
Identifiants: 99155124109311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article