Sensory Research in Göttingen

Moser, Tobias, Prof. Dr.

Professor of Auditory Neuroscience
- Dr. med. (M.D.), 1995, University of Jena
- Postdoctoral fellow with E. Neher at the MPI for Biophysical Chemistry, 1994 - 1997
- Group Leader at the Department of Otolaryngology, University of Göttingen since 1997
- Director of the Institute for Auditory Neuroscience, University Medical Center Göttingen, since 2015

Major Research Interests

The Institute for Auditory Neuroscience targets the molecular anatomy, physiology, pathophysiology and restoration of synaptic information processing in the auditory pathway. We aim to elucidate the specialized molecular and cellular mechanisms that enable information processing with at rates of hundreds per second over hours with submillisecond temporal precision. We combine complementary approaches to dissect the structure and function of hair cell ribbon synapses in the cochlea and of large calyceal central auditory synapses from the molecular level to systems function.

The hair cell synapse features a single and large ribbon-type active zone. When hair cells transduce the mechanical stimulus into an electrical signal, voltage-gated Ca2+ channels open and the ensuing Ca2+ influx triggers exocytosis of glutamate filled vesicles at the ribbon synapses. Our work on the hair cell ribbon synapse addresses fundamental questions such as ?How is the high temporal precision of the auditory code brought about by a chain of stochastic events at the hair cell synapse?? and ?How can a nanoscale membrane-domain turnover hundreds of vesicles without jamming and loss of molecular and structural identity? Evolved for speed, precision and inexhaustibility the synapse seems to employ intriguing synaptic mechanisms of Ca2+ channel-release site coupling, exocytosis, clearance from exocytosed material from the active zone and endocytic vesicle recycling as well as glutamate detection and action potential generation. Work over the past two decades has elucidated an unconventional molecular composition that likely explains the existence of genetic defects of the hair cell synapse (auditory synaptopathy) in humans, which leads to hearing impairment often in the absence of other symptoms. We work on developing gene therapeutic approaches to restore function in select cases of hereditary synaptopathy. For cases where such restoration of cochlear function is not emanable we aim improve the performance of cochlear implants by harnessing the potential of optogenetics for spatially more confined stimulation of the spiral ganglion. Finally, we have obtained evidence for major synaptic heterogeneity even within a given hair cell. We hypothesize that such synaptic heterogeneity enables the inner hair cell to decompose auditory information into functionally distinct neuronal channels to the brain.

Homepage Department/Research Group:

Selected Recent Publications

- Vogl C, Panou I, Yamanbaeva G, Wichmann C, Mangosing S, Vilardi F, Indzhykulian A, Pangrsic T, Santarelli R, Rodriguez-Ballesteros M, Weber T, Jung S, Cardenas E, Wu X, Wojcik SM, Kwan KY, del Castillo I, Schwappach B, Strenzke N, Corey DP, Lin SY, Moser T (2016) Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. EMBO J 2016 Jul 25 doi 10.15252/embj.201593565

- Ohn TL, Rutherford MA, Jing Z, Jung SY, Duque-Afonso CJ, Hoch G, Picher MM, Scharinger A, Strenzke N, Moser T (2016) Hair cells use active zones with different voltage-dependence of Ca2+-influx to decompose sounds into complementary neural codes. PNAS 2016 Jun 21. E4716?E4725, doi: 10.1073/pnas.1605737113

- Jung S, Maritzen T, Wichmann C, Jing Z, Neef A, Revelo NH, Al-Moyed H, Meese S, Wojcik SM, Panou I, Bulut H, Schu P, Ficner R, Reisinger E, Rizzoli SO, Neef J, Strenzke N, Haucke V, Moser T (2015) Disruption of adaptor protein 2? (AP-2?) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing. EMBO J. 2015 Oct 7. pii: e201591885

- Chapochnikov NM, Takago H, Huang CH, Pangr?i? T, Khimich D, Neef J, Auge E, Göttfert F, Hell SW, Wichmann C, Wolf F, Moser T (2014) Uniquantal Release through a Dynamic Fusion Pore Is a Candidate Mechanism of Hair Cell Exocytosis. Neuron. 2014 Sep 3, pii: S0896-6273(14)00678-3. doi: 10.1016/j.neuron.2014.08.003

- Hernandez VH, Gehrt A, Reuter K, Jing Z, Jeschke M, Mendoza Schulz A, Hoch G, Bartels M, Vogt G, Garnham CW, Yawo H, Fukazawa Y, Augustine GJ, Bamberg E, Kügler S, Salditt T, de Hoz L, Strenzke N, Moser T (2014) Optogenetic stimulation of the auditory pathway. J Clin Invest. 2014 Mar 3;124(3):1114-29. doi:10.1172/JCI69050

- Nouvian R, Neef J, Bulankina AV, Reisinger E, Pangr?i? T, Frank T, Sikorra S, Brose N, Binz T, Moser T (2011) Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins. Nat Neurosci. 2011 Apr;14(4):411-3. doi: 10.1038/nn.2774

- Frank T, Khimich D, Neef A, Moser T (2009) Mechanisms contributing to synaptic Ca2+ signals and their heterogeneity in hair cells. Proc Natl Acad Sci U S A 106:4483-4488.

- Meyer AC, Frank T, Khimich D, Hoch G, Riedel D, Chapochnikov NM, Yarin YM, Harke B, Hell S, Egner A, Moser T (2009) Tuning of synapse number, structure and function in the cochlea. Nat Neurosci 12:444-453.

- Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Perfettini I, Le Gall M, Rostaing P, Hamard G,Triller A, Avan P, Moser T, Petit C (2006) Otoferlin, defective in DFNB9 deafness, is essential for the Ca2+-triggered synaptic exocytosis at the auditory hair cell ribbon synapse. Cell 127:277-289.

- Khimich D, Nouvian R, Pujol R, tom Dieck S, Egner A, Gundelfinger ED, Moser T (2005) Hair cell synaptic ribbons are essential for synchronous auditory signaling. Nature 434:889-894.

- Brandt A, Khimich D, Moser T (2005) Few Ca_V 1.3 channels regulate a synaptic vesicle's exocytosis at the hair cell ribbon synapse. J Neurosci 25:11577-11585.