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 CaV1.3 – 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.
Highlights
IntroductionReceived: 11 January 2021 Accepted: February 2021Published: March 2021Front. Mol
Received: 11 January 2021 Accepted: February 2021Published: March 2021Citation: Krinner S, Predoehl F, Burfeind D, Vogl C and Moser T (2021) RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses.Front
Summary of statistical analysis of ABRs (Figure 3B): Wave I-V amplitudes were compared between RIM-BP1/2−/− (n = 7), RIM-BP2+/+ (n = 11) and RIM-BP2−/− (n = 8)
Summary
Received: 11 January 2021 Accepted: February 2021Published: March 2021Front. Mol. In mature mouse IHCs, neurotransmitter release from synaptic vesicles (SV) is controlled by the tight spatial coupling of CaV 1.3 voltage-gated L-type Ca2+channels and the SV release machinery (Brandt et al, 2005; Wong et al, 2014; Pangrsic et al, 2015). A small, defined SV pool with fast release kinetics, referred to as the readily releasable pool (RRP), is much less sensitive to the slow-binding Ca2+-buffer EGTA than to the fast-binding Ca2+-buffer BAPTA, emphasizing the Ca2+-nanodomain-like control of SV release (Moser and Beutner, 2000; Brandt et al, 2005; Pangrsic et al, 2015). There is evidence for Ca2+ nanodomain-like coupling in hair cells of other species, such as in frog auditory hair cells (Graydon et al, 2011), in rat IHCs
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