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.
Highlights
Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications
Optical cochlear implants-stimulating optogenetically modified SGNs, promise a fundamental advance of prosthetic sound coding by increasing frequency resolution, because light can be better confined than the electric field of electrodes[15]
For Optical cochlear implants (oCI) eventually to be translated into the clinic, opsins need to be delivered into the SGNs by postnatal virus application to the ear and should endow SGNs with high light-sensitivity and temporal fidelity of spike generation, while light scattering and blue light induced phototoxicity should be minimized
Summary
Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. 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. Fast channels need stronger light for the activation, high speed is indispensable for many optogenetic applications in neurobiology because many types of neurons operate at high firing rates in the intact animal. Optical cochlear implants (oCI)-stimulating optogenetically modified SGNs, promise a fundamental advance of prosthetic sound coding by increasing frequency resolution, because light can be better confined than the electric field of electrodes[15]. Adverse effects of optogenetic stimulation using blue light, the already available, fast blue light-activated ChR variants like ChETA (τoff = 4.4 ms9) and Chronos (τoff = 3.6 ms6) might have a limited applicability in animals and future clinical translation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
