Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings

Michael, Maria; Wolf, Bettina Julia; Klinge-Strahl, Astrid; Jeschke, Marcus; Moser, Tobias; Dieter, Alexander

doi:10.1016/j.brs.2023.09.018

Cited by 2 publications

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants

Thirumalai,

Henseler,

Enayati

et al. 2024

Preprint

View full text Add to dashboard Cite

Optogenetic stimulation has become a promising approach for restoring lost body function. For example, partial restoration of vision has been achieved in a blind patient and proof-of-concept has been demonstrated for optogenetic hearing restoration in rodents. In order to prepare clinical translation of hearing restoration, efficient and safe optogenetic modification of spiral ganglion neurons (SGNs) in the mature cochlea remains to be developed. Here, we established microcatheter-based administration adeno-associated virus (AAV) to scala tympani of the cochlea of Mongolian gerbils and compared it to the previously developed AAV-injection into the spiral ganglion. We probed the potential AAV-PHP.S capsid to express channelrhodopsins (ChRs) under the control of the human synapsin promotor in mature SGNs in hearing and deafened gerbils. Using the microcatheter approach, but not with the AAV-modiolus injection, we achieved reliable ChR expression in SGN enabling optogenetic stimulation of the auditory pathway in 80% of the treated animals. Yet, the efficiency of SGN transduction was modest with only ~30% ChR-expressing SGNs. Moreover, we encountered off-target expression in hair cells in hearing gerbils in both approaches, but not ChR expression in the central nervous system using microcatheter administration. Comparing optogenetic auditory brainstem responses of gerbils with and without hair cell transduction confirmed that SGNs were the primary site of optogenetic stimulation of the pathway.

show abstract

Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants

Thirumalai,

Henseler,

Enayati

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Toward Optogenetic Hearing Restoration

Huet,

Mager,

Gossler

et al. 2024

Annual Review of Neuroscience

View full text Add to dashboard Cite

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises to transfer more sound frequency information, hence improving hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of optogenetic hearing restoration and outline remaining challenges en route to clinical translation.

show abstract

Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings

Cited by 2 publications

References 48 publications

Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants

Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants

Toward Optogenetic Hearing Restoration

Contact Info

Product

Resources

About