Krinner Stefanie, Predoehl Friederike, Burfeind Dinah, Vogl Christian, Moser Tobias
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Collaborative Research Center 1286, University of Göttingen, Göttingen, Germany.
Front Mol Neurosci. 2021 Mar 23;14:651935. doi: 10.3389/fnmol.2021.651935. eCollection 2021.
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 ( ) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 ( ). Patch-clamp recordings from IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in IHCs. In contrast, the reduction of Ca-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.
内毛细胞（IHC）与螺旋神经节神经元之间的传入突触经过特殊分化，能够在较长时间内以亚毫秒级的精度忠实地编码声音。在此，我们研究了Rab3相互作用分子结合蛋白（RIM-BP）1和2（已知为活性区的多结构域蛋白，可直接与RIMs、巴松管和Ca 1.3相互作用）在IHC突触前功能和听力中的作用。听性脑干反应和耳声发射记录显示，小鼠中RIM-BPs 1和2的基因破坏（ ）导致的突触性听力损伤超过了缺乏RIM-BP2的小鼠（ ）。来自IHC的膜片钳记录表明，在 IHC中未观察到的突触小泡易释放池的胞吐作用存在细微损伤。相比之下，Ca内流的减少和持续胞吐作用与RIMBP2 IHC中的情况相似。我们得出结论，在IHC突触处正常的声音编码需要这两种RIM-BPs，其中RIM-BP2似乎起主导作用。
