f-Chrimson and vf-Chrimson, two ultrafast variants of the red-light activated channelrhodopsin Chrimson

Scientists from the Max-Planck-Institute of Biophysics in Frankfurt report that fast gating can be conferred to ChRs by helix 6 (helix F) mutation and demonstrate the application of fast red-shifted ChRs driving high spiking rates, enabling neural stimulation with very high firing frequencies and the temporal fidelity with low thresholds for stimulus intensity and duration. Efficient virus-mediated delivery and expression of a fast Chrimson mutant, designated f-Chrimson, in spiral ganglion neurons (SGNs) of mice, show that single-channel optical cochlea implants enable near-physiological spike rates and spike timing in SGNs and restore auditory nerve activity in deaf mice.
f- Chrimson is of particular interest to the neurosciences due to its easy application, the red-shifted action spectrum and high membrane expression. The analysis of fast spiking interneurons of the cerebral cortex demonstrated that they enable the remote optical control of even the fastest neurons at their intrinsic physiological limits. Importantly, there was no evidence for neuron loss several months after injection resulting in little to no risk of phototoxicity given the red-shifted action spectrum of f-Chrimson. f-Chrimson is a promising candidate for future clinical optogenetic restoration of sensory functions such as restoration of vision.

Priority application was filed in June 2016 (WO2017207761). Nationalization in EP, US, CN, KR and JP.

• Mager, T., Lopez de la Morena, D., Senn, V. et al. High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics. Nat Commun 9, 1750 (2018). https://doi.org/10.1038/s41467-018-04146-3.
• Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., & Bamberg, E.: Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 13940-13945. (2003). https://doi.org/10.1073/pnas.1936192100