BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing
Adam J. Carlton,
Jing-Yi Jeng,
Fiorella C. Grandi,
Francesca De Faveri,
Ana E. Amariutei,
Lara De Tomasi,
Andrew O’Connor,
Stuart L. Johnson,
David N. Furness,
Steve D.M. Brown,
Federico Ceriani,
Michael R. Bowl,
Mirna Mustapha,
Walter Marcotti
Affiliations
Adam J. Carlton
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Jing-Yi Jeng
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Fiorella C. Grandi
Sorbonne Université, INSERM, Institute de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
Francesca De Faveri
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Ana E. Amariutei
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Lara De Tomasi
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Andrew O’Connor
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Stuart L. Johnson
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK
David N. Furness
School of Life Sciences, Keele University, Keele ST5 5BG, UK
Steve D.M. Brown
Mammalian Genetics Unit, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK
Federico Ceriani
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK
Michael R. Bowl
Mammalian Genetics Unit, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK
Mirna Mustapha
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK
Walter Marcotti
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK; Corresponding author
Summary: 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.
