AUTHOR=Krinner Stefanie , Predoehl Friederike , Burfeind Dinah , Vogl Christian , Moser Tobias 

TITLE=RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=14

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.651935

DOI=10.3389/fnmol.2021.651935

ISSN=1662-5099

ABSTRACT=<p>The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 – multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and Ca<sub><italic>V</italic></sub>1.3 – in IHC presynaptic function and hearing. Recordings of auditory brainstem responses and otoacoustic emissions revealed that genetic disruption of RIM-BPs 1 and 2 in mice (<italic>RIM-BP1/2<sup>–/–</sup></italic>) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 (<italic>RIM-BP2<sup>–/–</sup></italic>). Patch-clamp recordings from <italic>RIM-BP1/2<sup>–/–</sup></italic> IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in <italic>RIM-BP2<sup>–/–</sup></italic> IHCs. In contrast, the reduction of Ca<sup>2+</sup>-influx and sustained exocytosis was similar to that in RIMBP2<sup>–/–</sup> IHCs. We conclude that both RIM-BPs are required for normal sound encoding at the IHC synapse, whereby RIM-BP2 seems to take the leading role.</p>