Keynote Lecture

Prof. Dr. Tobias Moser
Institute for Auditory Neuroscience, University Medical Center Göttingen
Max-Planck-Institutes for Biophysical Chemistry & Experimental Medicine
German Primate Center Göttingen

Synaptic sound cooding: from molecular physiology to functional restauration

Sound encoding at the afferent synapses of inner hair cells (IHC) processes information at rates of hundreds per second over hours with submillisecond temporal precision. Each synapse drives a single spiral ganglion neuron to fire at high rates upon strong stimulation. Interestingly, their spontaneous and sound-evoked activity varies as the Ca2+ signaling at the presynaptic active zones within a given IHC. Hence, we propose IHCs vary the properties of their presynaptic Ca2+ channel clusters to decompose auditory information into functionally distinct neuronal channels for wide dynamic range coding. Synaptic sound encoding involves efficient use of presynaptic glutamate release for spike generation, whereby release of a single vesicle might suffice to trigger an action potential. The ribbon synapse of inner hair cells, employs an unconventional molecular composition that likely evolved to meet these high functional demands. For example, efficient vesicle replenishment to the active zone - required to sustain the high rates of sound encoding - depends on the ribbon and on otoferlin. Genetic defects affecting synaptic proteins of IHCs cause human auditory synaptopathy – a peculiar non-syndromic hearing impairment. Efforts are undertaken to replace defect genes for future viral gene therapy.