Cochlear Hair Cell Innervation is Dependent on a Modulatory Function of Semaphorin-3A


Cantu-Guerra HL, Papazian MR, Gorsky AL, Alekos NS, Caccavano A, Karagulyan N, Neef J, Vicini S, Moser T, Coate TM


Developmental Dynamics


Dev Dyn. 2022 Oct 25.


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. This article is protected by copyright. All rights reserved.


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