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

Carlton, Adam J; Jeng, Jing-Yi; Grandi, Fiorella C; De Faveri, Francesca; Amariutei, Ana E; De Tomasi, Lara; O'Connor, Andrew; Johnson, Stuart L; Furness, David N; Brown, Steve D M; Ceriani, Federico; Bowl, Michael R; Mustapha, Mirna; Marcotti, Walter

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. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.]

Citation

Carlton, A. J., Jeng, J.-Y., Grandi, F. C., De Faveri, F., Amariutei, A. E., De Tomasi, L., …Marcotti, W. (2024). BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing. Cell Reports, 43(4), Article 114025. https://doi.org/10.1016/j.celrep.2024.114025

• Journal Article Type: Article
• Acceptance Date: Mar 15, 2024
• Online Publication Date: Apr 1, 2024
• Publication Date: Apr 23, 2024
• Deposit Date: Apr 22, 2024
• Journal: Cell reports
• Print ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 4
• Article Number: 114025
• DOI: https://doi.org/10.1016/j.celrep.2024.114025
• Keywords: cochlea, ribbon synapses, NDMA receptors, afferent fibers, glutamate receptors, hair cell, hearing loss, post-synaptic density, development, CP: Neuroscience
• Public URL: https://keele-repository.worktribe.com/output/796621