Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants
Optogenetic stimulation of type I spiral ganglion neurons (SGNs) promises an alternative to the electrical stimulation by current cochlear implants (CIs) for improved hearing restoration by future optical CIs (oCIs). Most of the efforts in using optogenetic stimulation in the cochlea so far used ear...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.635897/full |
| _version_ | 1818347897167544320 |
|---|---|
| author | Antoine Tarquin Huet Antoine Tarquin Huet Tobias Dombrowski Tobias Dombrowski Tobias Dombrowski Vladan Rankovic Vladan Rankovic Vladan Rankovic Anupriya Thirumalai Anupriya Thirumalai Tobias Moser Tobias Moser Tobias Moser Tobias Moser |
| author_facet | Antoine Tarquin Huet Antoine Tarquin Huet Tobias Dombrowski Tobias Dombrowski Tobias Dombrowski Vladan Rankovic Vladan Rankovic Vladan Rankovic Anupriya Thirumalai Anupriya Thirumalai Tobias Moser Tobias Moser Tobias Moser Tobias Moser |
| author_sort | Antoine Tarquin Huet |
| collection | DOAJ |
| description | Optogenetic stimulation of type I spiral ganglion neurons (SGNs) promises an alternative to the electrical stimulation by current cochlear implants (CIs) for improved hearing restoration by future optical CIs (oCIs). Most of the efforts in using optogenetic stimulation in the cochlea so far used early postnatal injection of viral vectors carrying blue-light activated channelrhodopsins (ChRs) into the cochlea of mice. However, preparing clinical translation of the oCI requires (i) reliable and safe transduction of mature SGNs of further species and (ii) use of long-wavelength light to avoid phototoxicity. Here, we employed a fast variant of the red-light activated channelrhodopsin Chrimson (f-Chrimson) and different AAV variants to implement optogenetic SGN stimulation in Mongolian gerbils. We compared early postnatal (p8) and adult (>8 weeks) AAV administration, employing different protocols for injection of AAV-PHP.B and AAV2/6 into the adult cochlea. Success of the optogenetic manipulation was analyzed by optically evoked auditory brainstem response (oABR) and immunohistochemistry of mid-modiolar cryosections of the cochlea. In order to most efficiently evaluate the immunohistochemical results a semi-automatic procedure to identify transduced cells in confocal images was developed. Our results indicate that the rate of SGN transduction is significantly lower for AAV administration into the adult cochlea compared to early postnatal injection. SGN transduction upon AAV administration into the adult cochlea was largely independent of the chosen viral vector and injection approach. The higher the rate of SGN transduction, the lower were oABR thresholds and the larger were oABR amplitudes. Our results highlight the need to optimize viral vectors and virus administration for efficient optogenetic manipulation of SGNs in the adult cochlea for successful clinical translation of SGN-targeting gene therapy and of the oCI. |
| first_indexed | 2024-12-13T17:41:27Z |
| format | Article |
| id | doaj.art-25fd634c60004dc18a59574b7ff04caa |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-13T17:41:27Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-25fd634c60004dc18a59574b7ff04caa2022-12-21T23:36:44ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-03-011410.3389/fnmol.2021.635897635897Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear ImplantsAntoine Tarquin Huet0Antoine Tarquin Huet1Tobias Dombrowski2Tobias Dombrowski3Tobias Dombrowski4Vladan Rankovic5Vladan Rankovic6Vladan Rankovic7Anupriya Thirumalai8Anupriya Thirumalai9Tobias Moser10Tobias Moser11Tobias Moser12Tobias Moser13Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyAuditory Neuroscience and Optogenetics Laboratory, German Primate Center, Göttingen, GermanyInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, St. Elisabeth Hospital, Ruhr University Bochum, Bochum, GermanyCollaborative Research Center 889, University of Göttingen, Göttingen, GermanyInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyAuditory Neuroscience and Optogenetics Laboratory, German Primate Center, Göttingen, GermanyRestorative Cochlear Genomics Group, Auditory Neuroscience and Optogenetics Laboratory, German Primate Center, Göttingen, GermanyInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyGöttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, Göttingen, GermanyInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyAuditory Neuroscience and Optogenetics Laboratory, German Primate Center, Göttingen, GermanyCollaborative Research Center 889, University of Göttingen, Göttingen, GermanyMultiscale Bioimaging Cluster of Excellence (MBExC), University of Göttingen, Göttingen, GermanyOptogenetic stimulation of type I spiral ganglion neurons (SGNs) promises an alternative to the electrical stimulation by current cochlear implants (CIs) for improved hearing restoration by future optical CIs (oCIs). Most of the efforts in using optogenetic stimulation in the cochlea so far used early postnatal injection of viral vectors carrying blue-light activated channelrhodopsins (ChRs) into the cochlea of mice. However, preparing clinical translation of the oCI requires (i) reliable and safe transduction of mature SGNs of further species and (ii) use of long-wavelength light to avoid phototoxicity. Here, we employed a fast variant of the red-light activated channelrhodopsin Chrimson (f-Chrimson) and different AAV variants to implement optogenetic SGN stimulation in Mongolian gerbils. We compared early postnatal (p8) and adult (>8 weeks) AAV administration, employing different protocols for injection of AAV-PHP.B and AAV2/6 into the adult cochlea. Success of the optogenetic manipulation was analyzed by optically evoked auditory brainstem response (oABR) and immunohistochemistry of mid-modiolar cryosections of the cochlea. In order to most efficiently evaluate the immunohistochemical results a semi-automatic procedure to identify transduced cells in confocal images was developed. Our results indicate that the rate of SGN transduction is significantly lower for AAV administration into the adult cochlea compared to early postnatal injection. SGN transduction upon AAV administration into the adult cochlea was largely independent of the chosen viral vector and injection approach. The higher the rate of SGN transduction, the lower were oABR thresholds and the larger were oABR amplitudes. Our results highlight the need to optimize viral vectors and virus administration for efficient optogenetic manipulation of SGNs in the adult cochlea for successful clinical translation of SGN-targeting gene therapy and of the oCI.https://www.frontiersin.org/articles/10.3389/fnmol.2021.635897/fullearhearing restorationprostheticsgene therapyviruscochlear implant |
| spellingShingle | Antoine Tarquin Huet Antoine Tarquin Huet Tobias Dombrowski Tobias Dombrowski Tobias Dombrowski Vladan Rankovic Vladan Rankovic Vladan Rankovic Anupriya Thirumalai Anupriya Thirumalai Tobias Moser Tobias Moser Tobias Moser Tobias Moser Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants Frontiers in Molecular Neuroscience ear hearing restoration prosthetics gene therapy virus cochlear implant |
| title | Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants |
| title_full | Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants |
| title_fullStr | Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants |
| title_full_unstemmed | Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants |
| title_short | Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants |
| title_sort | developing fast red light optogenetic stimulation of spiral ganglion neurons for future optical cochlear implants |
| topic | ear hearing restoration prosthetics gene therapy virus cochlear implant |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.635897/full |
| work_keys_str_mv | AT antoinetarquinhuet developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT antoinetarquinhuet developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasdombrowski developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasdombrowski developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasdombrowski developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT vladanrankovic developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT vladanrankovic developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT vladanrankovic developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT anupriyathirumalai developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT anupriyathirumalai developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasmoser developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasmoser developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasmoser developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants AT tobiasmoser developingfastredlightoptogeneticstimulationofspiralganglionneuronsforfutureopticalcochlearimplants |