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6. Optogenetic stimulation of the auditory pathway

Author

Hernandez, Victor H., Gehrt, Anna, Reuter, Kirsten, Jing, Zhizi, Jeschke, Marcus, Schulz, Alejandro Mendoza, Hoch, Gerhard, Bartels, Matthias, Vogt, Gerhard, Garnham, Carolyn W., Yawo, Hiromu, Fukazawa, Yugo, Augustine, George J., Bamberg, Ernst, Kugler, Sebastian, Salditt, Tim, Hoz, Livia de, Strenzke, Nicola, and Moser, Tobias

Subjects
Physiological aspects, Research, Ear -- Physiological aspects, Hearing -- Research, Medical research, Neurons -- Physiological aspects, Medicine, Experimental
Abstract

Introduction The electrical cochlear implant (CI) is considered the most successful neuroprosthesis. Implanted in more than 200,000 hearing-impaired subjects worldwide, CIs enable open speech comprehension in the majority of users [...], Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics.

Published
2014
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17. Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents

Author

Keppeler, Daniel, primary, Schwaerzle, Michael, additional, Harczos, Tamas, additional, Jablonski, Lukasz, additional, Dieter, Alexander, additional, Wolf, Bettina, additional, Ayub, Suleman, additional, Vogl, Christian, additional, Wrobel, Christian, additional, Hoch, Gerhard, additional, Abdellatif, Khaled, additional, Jeschke, Marcus, additional, Rankovic, Vladan, additional, Paul, Oliver, additional, Ruther, Patrick, additional, and Moser, Tobias, additional

Published
2020
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27. Emerging approaches for restoration of hearing and vision

Author

Kleinlogel, Sonja, Vogl, Christian, Jeschke, Marcus, Neef, Jakob, and Moser, Tobias

Subjects
otorhinolaryngologic diseases, 610 Medicine & health, 3. Good health
Abstract

Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For long, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye and ear has generated hope for a fundamental improvement of vision and hearing restoration. To date, one gene therapy for the restoration of vision has been approved and undergoing clinical trials will broaden its application including gene replacement, genome editing, and regenerative approaches. Moreover, optogenetics, i.e. controlling the activity of cells by light, offers a more general alternative strategy. Over little more than a decade, optogenetic approaches have been developed and applied to better understand the function of biological systems, while protein engineers have identified and designed new opsin variants with desired physiological features. Considering potential clinical applications of optogenetics, the spotlight is on the sensory systems. Multiple efforts have been undertaken to restore lost or hampered function in eye and ear. Optogenetic stimulation promises to overcome fundamental shortcomings of electrical stimulation, namely poor spatial resolution and cellular specificity, and accordingly to deliver more detailed sensory information. This review aims at providing a comprehensive reference on current gene therapeutic and optogenetic research relevant to the restoration of hearing and vision. We will introduce gene-therapeutic approaches and discuss the biotechnological and optoelectronic aspects of optogenetic hearing and vision restoration

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