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.