Authors
Mukhopadhyay M, Modgekar R, Yang-Hood A, Ohlemiller KK, Militchin V, Xiao M, Shen Z, Rensing NR, Wong M, Lee SJ, Seal RP, Warchol ME, Maloney SE, Yuede CM, Rutherford MA, Pangrsic T
Journal
BioRxiv
Citation
bioRxiv 2025.10.15.682551.
Abstract
Quantal synaptic transmission in vestibular end-organs is glutamatergic. Although genetic deletion of Slc17a8 (termed Vglut3) leads to deafness in mice, the dependence of vestibular function on VGLUT3-mediated quantal transmission is unknown. Here, we investigated the vestibular phenotype of Vglut3-/- mice at the cellular, systems, and behavioral levels. The type-II vestibular hair cells (VHCs) in Vglut3+/+ mice were strongly immunoreactive for VGLUT3, while type-I VHCs showed poor immunoreactivity. In Vglut3-/- mice quantal synaptic transmission in utricular calyces was reduced in rate and amplitude by > 95%. In vivo recordings of spontaneous activity in the vestibular nerve revealed similar action potential rates and regularity in Vglut3+/+ and Vglut3-/- mice, suggesting a divergent underlying mechanism compared to the silent Vglut3-/- auditory nerve. In behavioral studies, Vglut3-/- mice did not exhibit considerable sensorimotor or balance deficits. Collectively, these data support the view that non-quantal transmission is the predominant mode of neurotransmission between type I VHCs and vestibular calyceal afferent neurons. We propose that non-quantal transmission alone underlies the apparently normal vestibular nerve physiology and behavioral function in Vglut3-/- mice.
