Cochlear hair cell innervation is dependent on a modulatory function of Semaphorin‐3A

2022 | journal article. A publication with affiliation to the University of Göttingen.

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​Cochlear hair cell innervation is dependent on a modulatory function of Semaphorin‐3A​
Cantu‐Guerra, H. L.; Papazian, M. R.; Gorsky, A. L.; Alekos, N. S.; Caccavano, A.; Karagulyan, N. & Neef, J.  et al.​ (2022) 
Developmental Dynamics, art. dvdy.548​.​ DOI: https://doi.org/10.1002/dvdy.548 

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Authors
Cantu‐Guerra, Homero L.; Papazian, Michael R.; Gorsky, Anna L.; Alekos, Nathalie S.; Caccavano, Adam; Karagulyan, Nare; Neef, Jakob ; Vicini, Stefano; Moser, Tobias ; Coate, Thomas M.
Abstract
Background Proper connectivity between type I spiral ganglion neurons (SGNs) and inner hair cells (IHCs) in the cochlea is necessary for conveying sound information to the brain in mammals. Previous studies have shown that type I SGNs are heterogeneous in form, function and synaptic location on IHCs, but factors controlling their patterns of connectivity are not well understood. Results During development, cochlear supporting cells and SGNs express Semaphorin-3A (SEMA3A), a known axon guidance factor. Mice homozygous for a point mutation that attenuates normal SEMA3A repulsive activity (Sema3aK108N) show cochleae with grossly normal patterns of IHC innervation. However, genetic sparse labeling and three-dimensional reconstructions of individual SGNs show that cochleae from Sema3aK108N mice lacked the normal synaptic distribution of type I SGNs. Additionally, Sema3aK108N cochleae show a disrupted distribution of GLUA2 postsynaptic patches around the IHCs. The addition of SEMA3A-Fc to postnatal cochleae led to increases in SGN branching, similar to the effects of inhibiting glutamate receptors. Ca2+ imaging studies show that SEMA3A-Fc decreases SGN activity. Conclusions Contrary to the canonical view of SEMA3A as a guidance ligand, our results suggest SEMA3A may regulate SGN excitability in the cochlea, which may influence the morphology and synaptic arrangement of type I SGNs.
Issue Date
2022
Journal
Developmental Dynamics 
Project
EXC 2067: Multiscale Bioimaging 
Organization
Klinik für Hals-Nasen-Ohrenheilkunde ; Universitätsmedizin Göttingen ; Max-Planck-Institut für Multidisziplinäre Naturwissenschaften 
Working Group
RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding) 
External URL
https://mbexc.uni-goettingen.de/literature/publications/604
ISSN
1058-8388
eISSN
1097-0177
Language
English
Sponsor
G. Harold and Leila Y. Mathers Charitable Foundation https://doi.org/10.13039/100001229
National Institute on Deafness and Other Communication Disorders https://doi.org/10.13039/100000055

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