Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells

Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9084-9093. doi: 10.1073/pnas.1818358116. Epub 2019 Apr 11.


Encoding the wide range of audible sounds in the mammalian cochlea is collectively achieved by functionally diverse type I spiral ganglion neurons (SGNs) at each tonotopic position. The firing of each SGN is thought to be driven by an individual active zone (AZ) of a given inner hair cell (IHC). These AZs present distinct properties according to their position within the IHC, to some extent forming a gradient between the modiolar and the pillar IHC side. In this study, we investigated whether signaling involved in planar polarity at the apical surface can influence position-dependent AZ properties at the IHC base. Specifically, we tested the role of Gαi proteins and their binding partner LGN/Gpsm2 implicated in cytoskeleton polarization and hair cell (HC) orientation along the epithelial plane. Using high and superresolution immunofluorescence microscopy as well as patch-clamp combined with confocal Ca2+ imaging we analyzed IHCs in which Gαi signaling was blocked by Cre-induced expression of the pertussis toxin catalytic subunit (PTXa). PTXa-expressing IHCs exhibited larger CaV1.3 Ca2+-channel clusters and consequently greater Ca2+ influx at the whole-cell and single-synapse levels, which also showed a hyperpolarized shift of activation. Moreover, PTXa expression collapsed the modiolar-pillar gradients of ribbon size and maximal synaptic Ca2+ influx. Finally, genetic deletion of Gαi3 and LGN/Gpsm2 also disrupted the modiolar-pillar gradient of ribbon size. We propose a role for Gαi proteins and LGN in regulating the position-dependent AZ properties in IHCs and suggest that this signaling pathway contributes to setting up the diverse firing properties of SGNs.

Keywords: Ca signal; Gαi protein; hearing; ribbon synapse; sound encoding.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / physiology
  • Cell Polarity / physiology*
  • Cochlea / metabolism
  • Female
  • Hair Cells, Auditory / metabolism
  • Hair Cells, Auditory, Inner / metabolism*
  • Hair Cells, Auditory, Inner / physiology
  • Hair Cells, Vestibular / metabolism
  • Hearing / physiology
  • Immunohistochemistry / instrumentation
  • Male
  • Mice
  • Mice, Knockout
  • Patch-Clamp Techniques / methods
  • Sound
  • Spiral Ganglion / metabolism
  • Synapses / metabolism*
  • Synapses / physiology


  • Calcium Channels, L-Type