High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics

Thomas Mager, David Lopez de la Morena, Verena Senn, Johannes Schlotte, Anna D´Errico, Katrin Feldbauer, Christian Wrobel, Sangyong Jung, Kai Bodensiek, Vladan Rankovic, Lorcan Browne, Antoine Huet, Josephine Jüttner, Phillip G. Wood, Johannes J. Letzkus, Tobias Moser () and Ernst Bamberg ()
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Thomas Mager: Max Planck Institute of Biophysics
David Lopez de la Morena: University Medical Center Göttingen
Verena Senn: Max Planck Institute for Brain Research
Johannes Schlotte: Max Planck Institute of Biophysics
Anna D´Errico: Max Planck Institute of Biophysics
Katrin Feldbauer: Max Planck Institute of Biophysics
Christian Wrobel: University Medical Center Göttingen
Sangyong Jung: University Medical Center Göttingen
Kai Bodensiek: University Medical Center Göttingen
Vladan Rankovic: University Medical Center Göttingen
Lorcan Browne: University Medical Center Göttingen
Antoine Huet: University Medical Center Göttingen
Josephine Jüttner: Friedrich Miescher Institute for Biomedical Research
Phillip G. Wood: Max Planck Institute of Biophysics
Johannes J. Letzkus: Max Planck Institute for Brain Research
Tobias Moser: University Medical Center Göttingen
Ernst Bamberg: Max Planck Institute of Biophysics

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration.

Date: 2018
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DOI: 10.1038/s41467-018-04146-3

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