BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing

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. [Display omitted] •In the mouse cochlea, BAI1 is expressed in the afferent spiral ganglion neurons (SGNs)•AMPA receptors are absent in the SGN afferent terminals of adult Bai1-deficient mice•Functional IHC ribbon synapses fail to relay sound information to SGNs in mice lacking BAI1•Bai1-deficient mice have highly elevated hearing thresholds Carlton et al. show that BAI1 is essential for activating SGN afferent terminals at cochlear IHC ribbon synapses. In Bai1-deficient mice, IHC-SGN synapses are formed but AMPA receptors that are normally in the post-synaptic density are either missing or uncoupled from the pre-synaptic ribbons, leading to highly raised hearing thresholds.