Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity

Cell. 2018 Aug 23;174(5):1229-1246.e17. doi: 10.1016/j.cell.2018.07.007. Epub 2018 Aug 2.


In the auditory system, type I spiral ganglion neurons (SGNs) convey complex acoustic information from inner hair cells (IHCs) to the brainstem. Although SGNs exhibit variation in physiological and anatomical properties, it is unclear which features are endogenous and which reflect input from synaptic partners. Using single-cell RNA sequencing, we derived a molecular classification of mouse type I SGNs comprising three subtypes that express unique combinations of Ca2+ binding proteins, ion channel regulators, guidance molecules, and transcription factors. Based on connectivity and susceptibility to age-related loss, these subtypes correspond to those defined physiologically. Additional intrinsic differences among subtypes and across the tonotopic axis highlight an unexpectedly active role for SGNs in auditory processing. SGN identities emerge postnatally and are disrupted in a mouse model of deafness that lacks IHC-driven activity. These results elucidate the range, nature, and origins of SGN diversity, with implications for treatment of congenital deafness.

Keywords: Vglut3; activity-dependent development; auditory; neuron heterogeneity; neuronal subtypes; single-cell RNA-seq; spiral ganglion neurons; spontaneous activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Acidic / genetics
  • Animals
  • Calbindin 2 / genetics
  • Cochlea / physiology
  • Deafness / genetics
  • Ear, Inner / physiology*
  • Female
  • Hair Cells, Auditory, Inner / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sensory Receptor Cells / physiology*
  • Sequence Analysis, RNA
  • Spiral Ganglion / physiology
  • Synaptic Transmission
  • Transgenes


  • Amino Acid Transport Systems, Acidic
  • Calb2 protein, mouse
  • Calbindin 2
  • vesicular glutamate transporter 3, mouse