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. Hüser, Svenja M Kiehn, Aida Garrido‐Charles, Alexander Meyer, Adrian Rambousky, Theocharis Alvanos, Isabel Witzke, Keila Dara Rojas-García, Martin D Draband, Lukas Cyganek, Eric Klein, Patrick Ruther, Antoine Huet, Stuart Trenholm, Émilie Macé, Kathrin Kusch, Tobias Bruegmann, Bettina Wolf, Thomas Mager, Tobias Moser
Abstract
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.