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Optogenetic modification of the auditory nerve with adeno-associated viral vectors
18 April 2018 (online)
While being the most successful neuroprosthesis, the restoration of hearing based on electrical stimulation of spiral ganglion neurons (SGNs) is technically limited in frequency resolution due to the spread of current. Our idea of replacing the electrical stimulation with spatially confined optical stimulation based on an optogenetic approach aims to encounter this limitation. Precondition for optogenetic stimulation is the expression of a light-sensitive ion channel in the SGNs forming the auditory nerve (AN).
We chose the Mongolian Gerbil (Meriones unguiculatus) as a model organism. A genetically modified variant of the red-shifted Opsin Chrimson (f-Chrimson) with synapsin promotor was tested for expression in the AN at different time-points, with different methods of injection and packed in different adeno-associated viral vectors (AAV). This evaluation was done histologically and with different electrophysiological approaches. For optical stimulation, we used a 594nm laser system with a single optical fiber in the round window.
We saw a clear influence of the transduction depending on the adult or early postnatal injection. The transduction efficacy of adult SGNs could be improved using novel AAV-based viral vectors (AAV.anc80/AAV.PHP.B) instead of AAV2/6. We could further demonstrate the fast optogenetic activation at different levels of the auditory pathway.
In summary, advances in developing AAV vectors offer to improve the efficacy of optogenetic modification of SGNs. The fast activation of the auditory pathway with f-chrimson is promising for the future development of optogenetic cochlear implants.