RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses
Stefanie Krinner1,2,3, Friederike Predoehl1, Dinah Burfeind4
1Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Abstract:
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 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 (RIM-BP1/2 ) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 (RIM-BP2 ). Patch-clamp recordings from RIM-BP1/2 IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in RIM-BP2 IHCs. In contrast, the reduction of Ca2+-influx and sustained exocytosis was similar to that in RIMBP2-/- 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.
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