scholarly journals Author response: Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons

2015 ◽  
Author(s):  
Thomas M Coate ◽  
Nathalie A Spita ◽  
Kaidi D Zhang ◽  
Kevin T Isgrig ◽  
Matthew W Kelley
eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Thomas M Coate ◽  
Nathalie A Spita ◽  
Kaidi D Zhang ◽  
Kevin T Isgrig ◽  
Matthew W Kelley

Auditory function is dependent on the formation of specific innervation patterns between mechanosensory hair cells (HCs) and afferent spiral ganglion neurons (SGNs). In particular, type I SGNs must precisely connect with inner HCs (IHCs) while avoiding connections with nearby outer HCs (OHCs). The factors that mediate these patterning events are largely unknown. Using sparse-labeling and time-lapse imaging, we visualized for the first time the behaviors of developing SGNs including active retraction of processes from OHCs, suggesting that some type I SGNs contact OHCs before forming synapses with IHCs. In addition, we demonstrate that expression of Semaphorin-3F in the OHC region inhibits type I SGN process extension by activating Neuropilin-2 receptors expressed on SGNs. These results suggest a model in which cochlear innervation patterns by type I SGNs are determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal that impedes processes from extending beyond the IHC region.


2019 ◽  
Vol 39 (27) ◽  
pp. 5284-5298 ◽  
Author(s):  
Hanna E. Sherrill ◽  
Philippe Jean ◽  
Elizabeth C. Driver ◽  
Tessa R. Sanders ◽  
Tracy S. Fitzgerald ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183773 ◽  
Author(s):  
Tian Yang ◽  
Jennifer Kersigo ◽  
Shu Wu ◽  
Bernd Fritzsch ◽  
Alexander G. Bassuk

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Lars Becker ◽  
Michael E Schnee ◽  
Mamiko Niwa ◽  
Willy Sun ◽  
Stephan Maxeiner ◽  
...  

The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon’s contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles.


2019 ◽  
Vol 116 (18) ◽  
pp. 9084-9093 ◽  
Author(s):  
Philippe Jean ◽  
Özge Demet Özçete ◽  
Basile Tarchini ◽  
Tobias Moser

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.


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