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Series GSE242669 Query DataSets for GSE242669
Status Public on Sep 27, 2024
Title The upregulation of K+ and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca2+ action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals. The role of spontaneous IHC activity in the refinement of SGN characteristics is still largely unknown. Using pre-hearing otoferlin knockout mice (Otof-/-), in which Ca2+-dependent exocytosis in IHCs is abolished, we found that developing SGNs fail to upregulate low-voltage-activated K+-channels and hyperpolarisation-activated cyclic-nucleotide-gated channels. This delayed maturation resulted in hyperexcitable SGNs with immature firing characteristics. We have also shown that SGNs that synapse with the pillar side of the IHCs selectively express a resurgent K+ current, highlighting a novel biophysical marker for these neurons. RNA-sequencing showed that several K+ channels are downregulated in Otof-/- mice, further supporting the electrophysiological recordings. Our data demonstrate that spontaneous Ca2+-dependent activity in pre-hearing IHCs regulates some of the key biophysical and molecular features of the developing SGNs. KEY POINTS: Ca2+-dependent exocytosis in inner hair cells (IHCs) is otoferlin-dependent as early as postnatal day 1. A lack of otoferlin in IHCs affects potassium channel expression in SGNs. The absence of otoferlin is associated with SGN hyperexcitability. We propose that type I spiral ganglion neuron functional maturation depends on IHC exocytosis.
 
Overall design Cochlear Tissue was dissected from heterzygous and homozygous otof KO mice and submitted for RNA-sequencing. Both pairs of cochleas from 2-3 P7 pups were pooled for each genotype. (n=2 pools per genotype). Sampels were dissected in the same manner as used for all patching experiments. RNA-seq data was analyzed using the nf-core pipeline and differential expression testing was performed using DeSEQ2.
 
Contributor(s) Grandi F, Mustapha M
Citation(s) 39324853
Submission date Sep 07, 2023
Last update date Sep 27, 2024
Contact name Fiorella Grandi
E-mail(s) fiorella.grandi0@gmail.com
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 (4)
GSM7766606 Otof_het_Rep1
GSM7766607 Otof_het_Rep2
GSM7766608 Otof_hom_Rep1
Relations
BioProject PRJNA1013999

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Supplementary file Size Download File type/resource
GSE242669_DEGsOtofKOP7.xlsx 45.4 Kb (ftp)(http) XLSX
GSE242669_Otof_salmon_genecounts.tsv.gz 229.1 Kb (ftp)(http) TSV
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