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Series GSE254269 Query DataSets for GSE254269
Status Public on Mar 27, 2024
Title BAI1 localises AMPA receptors at the cochlear afferent postsynaptic density and is
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming axo-somatic synapses with inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea. Although IHC ribbon synapses have been extensively studied, the molecular mechanisms regulating the structure and function of the post-synaptic density (PSD) at the SGN afferent terminals are largely unknown. Using functional, morphological, and transcriptomic approaches, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1), encoded by the Adgrb1 gene, is required for the clustering of the glutamate AMPA receptors GluR2-4 to the SGN post-synaptic density. Adult mice expressing BAI1 lacking the N-terminal thrombospondin type 1 repeats (TRS) have functional IHC synapses but fail to transmit acoustic information to the SGNs, leading to highly raised auditory thresholds. We also found that in adult Bai1-deficient mice, despite the almost complete absence of AMPA receptors, the SGN fibres innervating the IHCs did not degenerate. RNA sequencing and western blotting also indicate that AMPA receptors are expressed in the cochlea of Bai1-deficient mice, highlights that BAI1 is involved is trafficking or anchoring GluR2-4 to the PSDs. Moreover, these results have identified novel molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.
Overall design The sensory epithelium and spiral ganglion neurons from 4 mice were micro dissected in DNase free ice-cold PBS 1X and immediately snap frozen in liquid nitrogen. Two batches of 3 and 4 replicates (P7) and one batch of 3 replicates (P22) from each genotype.
Contributor(s) Grandi F, Carlton A, Jeng J, Marcotti W
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Submission date Jan 25, 2024
Last update date Mar 27, 2024
Contact name Fiorella Grandi
Organization name Sorbonne Universite
Department Centre de Recherche de Myologie
Lab UMRS 974
Street address 105 Bld d'Hopital
City Paris
ZIP/Postal code 75013
Country France
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (20)
GSM8037043 Bai1KO_P22_Het_Rep1
GSM8037044 Bai1KO_P22_Het_Rep2
GSM8037045 Bai1KO_P22_Het_Rep3
BioProject PRJNA1069109

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Supplementary file Size Download File type/resource
GSE254269_salmon_counts_P22.tsv.gz 301.8 Kb (ftp)(http) TSV
GSE254269_salmon_counts_P7.csv.gz 442.3 Kb (ftp)(http) CSV
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