Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System

Shuohao Sun, Travis Babola, Gabriela Pregernig, Kathy S. So, Matthew Nguyen, Shin San M. Su, Adam T. Palermo, Dwight E. Bergles, Joseph C. Burns, Ulrich Müller

Research output: Contribution to journalArticle

Abstract

Type I spiral ganglion neurons (SGNs) transmit sound information from cochlear hair cells to the CNS. Using transcriptome analysis of thousands of single neurons, we demonstrate that murine type I SGNs consist of subclasses that are defined by the expression of subsets of transcription factors, cell adhesion molecules, ion channels, and neurotransmitter receptors. Subtype specification is initiated prior to the onset of hearing during the time period when auditory circuits mature. Gene mutations linked to deafness that disrupt hair cell mechanotransduction or glutamatergic signaling perturb the firing behavior of SGNs prior to hearing onset and disrupt SGN subtype specification. We thus conclude that an intact hair cell mechanotransduction machinery is critical during the pre-hearing period to regulate the firing behavior of SGNs and their segregation into subtypes. Because deafness is frequently caused by defects in hair cells, our findings have significant ramifications for the etiology of hearing loss and its treatment. Single-cell analyses of mouse type I spiral ganglion neurons characterize three functionally distinct subtypes, revealing insights into auditory processing with implications for treating congenital deafness.

Original languageEnglish (US)
Pages (from-to)1247-1263.e15
JournalCell
Volume174
Issue number5
DOIs
StatePublished - Aug 23 2018

Keywords

  • hair cell
  • mechanotransduction
  • neuronal diversity
  • neuronal subtypes
  • single-cell RNA sequencing
  • spiral ganglion neuron
  • spontaneous activity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Sun, S., Babola, T., Pregernig, G., So, K. S., Nguyen, M., Su, S. S. M., Palermo, A. T., Bergles, D. E., Burns, J. C., & Müller, U. (2018). Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System. Cell, 174(5), 1247-1263.e15. https://doi.org/10.1016/j.cell.2018.07.008