Cochlear implants partially restore hearing via direct electrical stimulation of spiral ganglion neurons (SGNs). However, spread of excitation from each electrode limits spectral coding. We explored the use of optogenetics to deliver spatially restricted and cell-specific excitation in the cochlea of adult Mongolian gerbils. Adeno-associated virus carrying the gene encoding the light-sensitive calcium translocating channelrhodopsin (CatCh) was injected into the cochlea of adult gerbils. SGNs in all cochlea turns showed stable and long-lasting CatCh expression, and electrophysiological recording from single SGNs showed that light stimulation up to few hundred Hertz induced neuronal firing. We characterized the light-induced activity in the auditory pathway by electrophysiological and behavioral analysis. Light- and sound-induced auditory brainstem responses showed similar kinetics and amplitude. In normal hearing adult gerbils, optical cochlear implants elicited stable optical auditory brainstem responses over a period of weeks. In normal hearing animals, light stimulation cued avoidance behavior that could be reproduced by subsequent acoustic stimulation, suggesting similar perception of light and acoustic stimuli. Neurons of the primary auditory cortex of normal hearing adult gerbils responded with changes in firing rates with increasing light intensity. In deaf adult gerbils, light stimulation generated auditory responses and cued avoidance behavior indicating partial restoration of auditory function. Our data show that optogenetic cochlear stimulation achieved good temporal fidelity with low light intensities in an adult rodent model, suggesting that optogenetics might be used to develop cochlear implants with improved restorative capabilities.

Optogenetic tools, providing non‐invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temporal fidelity pertinent to auditory coding because they require milliseconds to close after light‐off. Here, we biophysically characterized the fast channelrhodopsin Chronos and revealed a deactivation time constant of less than a millisecond at body temperature. In order to enhance neural expression, we improved its trafficking to the plasma membrane (Chronos‐ES/TS). Following efficient transduction of SGNs using early postnatal injection of the adeno‐associated virus AAV‐PHP.B into the mouse cochlea, fiber‐based optical stimulation elicited optical auditory brainstem responses (oABR) with minimal latencies of 1 ms, thresholds of 5 μJ and 100 μs per pulse, and sizable amplitudes even at 1,000 Hz of stimulation. Recordings from single SGNs demonstrated good temporal precision of light‐evoked spiking. In conclusion, efficient virus‐mediated expression of targeting‐optimized Chronos‐ES/TS achieves ultrafast optogenetic control of neurons.

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