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

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

Jean P1,2,3,4,5, Özçete ÖD1,2,3,5,6, Tarchini B7,8,9, Moser T10,2,3,5,11.

Author information

1
Institute for Auditory Neuroscience, University Medical Center Göttingen, 37075 Göttingen, Germany.
2
InnerEarLab, University Medical Center Göttingen, 37075 Göttingen, Germany.
3
Collaborative Research Center 889, University of Göttingen, 37075 Göttingen, Germany.
4
Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37075 Göttingen, Germany.
5
Auditory Neuroscience Group, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
6
International Max Planck Research School Neuroscience, Göttingen Graduate School for Neuroscience and Molecular Biosciences, University of Göttingen, 37073 Göttingen, Germany.
7
The Jackson Laboratory, Bar Harbor, ME 04609; basile.tarchini@jax.org tmoser@gwdg.de.
8
Department of Medicine, Tufts University, Boston, MA 02111.
9
Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469.
10
Institute for Auditory Neuroscience, University Medical Center Göttingen, 37075 Göttingen, Germany; basile.tarchini@jax.org tmoser@gwdg.de.
11
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, 37075 Göttingen, Germany.

Abstract

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

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