Abstract：
Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.
摘要：
I型螺旋神经节神经元（SGN）通过与哺乳动物耳蜗中的内毛细胞（IHC）形成突触来将声音信息传递到中枢听觉通路。调控SGN传入末端突触后密度（PSD）形成的分子机制尚不清楚。这里,我们证明，脑特异性血管生成抑制剂1（BAI1）是PSD上AMPA受体GluR2-4（谷氨酸受体2-4）聚集所必需的。成年Bai1缺陷小鼠具有功能性IHC，但无法将信息传输到SGN，导致听力阈值大幅提高。尽管几乎完全不存在AMPA受体亚基，支配IHC的SGN纤维不会退化。此外，我们表明AMPA受体仍然在Bai1缺陷小鼠的耳蜗中表达，强调BAI1在贩运或将GluR2-4锚定到PSD中的作用。这些发现确定了耳蜗带状突触处声音编码所需的分子和功能机制。
