Persistence of vestibular function in the absence of glutamatergic transmission from hair cells.

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.