Research ArticleOPTOGENETICS

Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils

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Science Translational Medicine  11 Jul 2018:
Vol. 10, Issue 449, eaao0540
DOI: 10.1126/scitranslmed.aao0540

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Listening to light

Cochlear implants rely on electrical stimulation of the auditory nerve to provide a sense of sound to a person with severe hearing loss. However, the resolution of complex sounds is limited by the spreading of the current around the electrode. Wrobel et al. leveraged optogenetics to develop an optical cochlear implant that uses light for spatially and temporally precise stimulation of the auditory nerve in deaf adult gerbils. After virus-mediated expression of a light-sensitive protein in cochlear neurons, the optical implant was able to stimulate the auditory pathway and restored auditory-driven behavior in deaf gerbils. Further studies testing the resolution potential of optical cochlear implants are warranted.

Abstract

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.

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