Auditory Neuroscience and Optogenetics Laboratory

An optical cochlear implant compared with an electrical cochlear implant.

Our brains must make sense of the myriad sensations that all of us face each and every day to successfully find one’s bearings in life. We need to categorize, learn, remember, adapt, pay attention etc. in order to appropriately react and act in our environments. The auditory system is a particularly fascinating example of these feats as we e.g. use speech heavily to infer about our social environment and to interact with others. The Auditory Neuroscience and Optogenetics (ANO) Laboratory studies how the auditory system processes acoustic information in normal hearing and aims to improve hearing restoration for the deaf.

Considering that approximately 5% of the world’s population requires treatment of hearing impairment there is a major unmet clinical need for improved hearing restoration beyond current hearing aids and cochlear implants. Therefore, we are working with marmoset monkeys for late preclinical studies on gene therapy and optical cochlear implants which builds on pioneering work in rodents performed at the Institute for Auditory Neuroscience of the University Medical Center. We chose to work with marmosets as a non-human primate model that is amenable to genetic manipulation, has a rich vocal communication and also for this reason has attracted interest of auditory neuroscientists. We have established virus administration and cochlear implant surgery as well as physiological and behavioural analysis of hearing in marmosets.

In collaboration with the Behr lab (ref. for GFP marmoset) we are working toward modelling human genetic hearing impairment. We are currently focusing on auditory synaptopathy caused by mutations in the OTOF gene that encodes for the hair cell protein otoferlin. There is great hope that OTOF-related hearing impairment can be cured by AAV-mediated gene therapy based on partial restoration of auditory function in mouse models (Al‐Moyed et al, 2019; Akil et al, 2019; Rankovic et al, 2021). Nonetheless, much remains to be done to translate these approaches into a clinical application. We aim to contribute to this important effort by first optimizing the gene therapy approach in mice and then translating it to the newly generated marmoset model OTOF-related hearing impairment.

The cochlear implant, used worldwide by more than 700.000 hearing impaired people, typically enables open speech understanding and is considered the most successful neuroprosthesis. Nonetheless, listening in noisy environments as well as music appreciation remain challenging mostly because of the poor frequency and intensity resolution that results from broad current spread from of each of the 1-2 dozens of electrode contacts (see image above: Electrical Cochlear Implant). Since light can be conveniently confined in space, using optogenetic stimulation of the spiral ganglion of the cochlea promises a fundamental improvement of frequency and intensity coding compared to that achievable with electrical cochlear implants. In our preclinical work with rodents and marmosets, we are developing gene therapy and optical cochlear implants for future clinical optogenetic hearing restoration. Collaboration with academic partners in Freiburg and Chemnitz as well as with industry (OptoGenTech and MED-EL) is of paramount importance to accomplish this task.

As a faculty member at, both, German Primate Center and University Medical Center Göttingen (UMG), Tobias heads the Auditory Neuroscience and Optogenetics Laboratory. The Moser group aims to develop the optical cochlear implant as well as gene therapy for OTOF-related hearing impairment in collaboration with the groups of Dr. Jeschke and Dr. Kusch as well as with the Dept. of Otolaryngology chaired by Dr. Beutner of UMG, the group of Dr. Schwarz (Chemnitz) and the group of Dr. Ruther (Freiburg). His group at the German Primate Center contributes audiological testing of normal and restored hearing and works towards hard and software development for preclinical optical and electrical cochlear implants.

Fig. 1. Linear array of micro-light emitting diodes (µLED) generated by Schwarz, Ruther and colleagues in Freiburg. Image: Christian Gossler

Fig. 2. Upscaled 3D-printed model of the mouse cochlea based on x-ray tomography data. Image: Daniel Keppeler

Publications

Keppeler D, Kampshoff C, Thirumalai A, Duque-Afonso CJ, Schaeper J, Quilitz T, Töpperwien M, Vogl C, Hessler R, Meyer A, Salditt T, Moser T (2021) Multiscale photonic imaging of the native and implanted cochlea. PNAS, https://doi.org/10.1073/pnas.2014472118

Huet AT, Bali B, Lopez de la Morena D, Rankovic V, Mittring A, Mager T, Moser T. Utility of red-light ultrafast optogenetic stimulation of the auditory pathway. EMBO Molecular Medicine, 2021, in press

Huet AT, Dombrowski T, Rankovic V, Thirumalai A, Moser T. Developing fast, red-light optogenetic stimulation of spiral ganglion neurons for future optical cochlear implants . Frontiers in Molecular Neuroscience, 2021 January 7th; 13:253. doi: 10.3389/fnmol.2020.600051

Rankovic V, Vogl C, Dörje NM, Bahader I, Duque-Afonso CJ, Thirumalai A, Weber T, Kusch K, Strenzke N, Moser T. Overloaded adeno-associated virus as a novel gene therapeutic tool for otoferlin-related deafness

Wrobel C, Zafeiriou M-P, Moser T. Understanding and Treating Paediatric Hearing Impairment. EBioMedicine, 2021 January 7th Volume 63, 103171

Jeschke M, Happel MFK, Tziridis K, Krauss P, Schilling A, Schulze H, Ohl FW. Acute and Long-Term Circuit-Level Effects in the Auditory Cortex After Sound Trauma. Frontiers in Neuroscience, 2021 January 5th;14:598406. doi: 10.3389/fnins.2020.598406

Zabelski D, Alekseev A, Kovalev K, Rankovic V, Balandin T, Soloviov D, Bratanov D, Saveljeva E, Podolyak E, Vokov D, Vaganova S, Astashkin R, Chizov I, Yutin N, Rulev M, Popov A, Eria-Oliveria A-S, Rokitskay T, Mager T, Antonenko Y, Rosselli R, Armeev G, Shaitan K, Vivaudou M, Büldt G, Rogachev A, Rodriguez-Valera F, Kripchnikov M, Moser T, Offenhäuser A, Willbold D, Koonin E, Bamberg E, Gordeliy V. Viral rhodopsins 1 are an unique family of light-gated cation channels. Nature Communications 2020 Nov 11;11(1):5707. doi: 10.1038/s41467-020-19457-7

Keppeler D, Schwaerzle M, Harczos T, Jablonski L, Dieter A, Wolf B, Ayub S, Vogl C, Wrobel C, Hoch G, Abdellatif K, Jeschke M, Rankovic V, Paul O, Ruther P, Moser T. Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents. EMBO Molecular Medicine, 2020 Jun 29; e12387. doi: 10.15252

Dieter A, Klein E, Keppeler D, Jablonski L, Harczos T, Hoch G, Rankovic V, Paul O, Jeschke M, Ruther P, Moser T. μLED-based optical cochlear implants for spectrally selective activation of the auditory nerve

Kleinlogel* S, Vogl* C, Jeschke* M, Neef J, Moser T (2020) Emerging approaches for restoration of hearing and vision. Physiological Reviews, Available at: https://doi.org/10.1152/physrev.00035.2019.
* Equal contribution.

Dieter A, Keppeler D, Moser, T. Towards the Optical Cochlear Implant: Optogenetic Approaches for Hearing Restoration, EMBO Molecular Medicine, 2020 Mar 30. e11618, doi.10.15252/emmm.201911618

Moser T, Dieter A. Towards optogenetic approaches for hearing restoration, Science Direct, Biochemical and Biophysical Research Communications: 10.1016/j.bbrc. 2019.12.126, February 2020.

Dieter A, Duque Afonso CJ, Rankovic V, Jeschke M, Moser T. Near physiological spectral selectivity of cochlear optogenetics. Nature Communications, 2019 10(1): 1962, doi: 10.1038/s41467-019-09980-7

Keppeler D, Martins Merino R, Lopez de la Morena D, Bali B, Huet A T, Gehrt A, Wrobel C, Subramanian S, Dombrowski T, Wolf F, Rankovic V, Neef A, Moser T. Ultrafast optogenetic stimulation of the auditory pathway by targeting-optimized Chronos. EMBO Journal, November 2018.

Dombrowski T, Rankovic V, Moser T. Towards the optical cochlear implant. Cold Spring Harbor Laboratory Press October 2018.

Wrobel C, Dieter A, Huet A, Keppeler D, Duque-Afonso C J, Vogl C, Hoch G, Jeschke M, Moser T. Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils. Sci Transl Med. 2018: 10(449): eaao0540. doi: 10.1126/scitranslmed.aao0540

Mager T, de la Morena D, Senn V, Schlotte J, D´Errico A, Feldbauer K, Wrobel C, Jung S, Bodensiek K, Rankovic V, Browne L, Huet A, Jüttner J, Wood P, Letzkus J, Moser T, Bamberg E (2018) High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics.
Nature Communications 2018 9(1):1750 doi: 10.1038/s41467-018-04146-3.

Gossler, C., Bierbrauer, C., Moser, R., Kunzer, M., Holc, K., Koehler, K., Wagner, J., Schwaerzle, M., Ruther, P., Paul, O., et al. (2014) GaN-based micro-LED arrays on flexible substrates for optical cochlear implants. Journal of Physics D: Appl. Phys. 47 205401 doi:10.1088/0022-3727/47/20/205401

Hernandez, V.H., Gehrt, A., Reuter, K., Jing, Z., Jeschke, M., Mendoza Schulz, A., Hoch, G., Bartels, M., Vogt, G., Garnham, C.W., et al. (2014). Optogenetic stimulation of the auditory pathway. J. Clin. Invest. 124, 1114–1129. http://www.jci.org/articles/view/69050

Hernandez VH, Gehrt A, Jing Z, Hoch G, Jeschke M, Strenzke N, Moser T. Optogenetic stimulation of the auditory nerve. J Vis Exp. 2014 Oct 8;(92):e52069. http://stm.sciencemag.org/content/10/449/eaao0540

Jeschke M, Moser T. Considering optogenetic stimulation for cochlear implants. Hear Res. 2015 Apr;322:224-234. doi: 10.1016/j.heares.2015.01.005. Epub 2015 Jan 16. Review. PMID: 25601298

Moser T. Optogenetic stimulation of the auditory pathway for research and future prosthetics. Curr Opin Neurobiol. 2015 Jan 28;34C:29-36. doi: 10.1016/j.conb.2015.01.004. [Epub ahead of print] Review. PMID: 25637880

Moser T, Vogl C. New insights into cochlear sound encoding [version 1; referees: 2 approved]. F1000Research 2016, 5(F1000 Faculty Rev):2081 (doi: 10.12688/f1000research.8924.1)