Persistence of vestibular function in the absence of glutamatergic transmission from hair cells
Quantal synaptic transmission in vestibular endorgans is glutamatergic. Here, we investigated the vestibular phenotype of deaf Vglut3<sup>-/-</sup> (Slc17a8<sup>-/-</sup>) mice from the cellular to behavioral levels. In Vglut3<sup>-/-</sup> 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 no significant effect of VGLUT3 deletion on afferent rate and regularity, suggesting a divergent underlying mechanism compared to the silent Vglut3<sup>-/-</sup> auditory nerve. In behavioral studies, Vglut3<sup>-/-</sup> mice did not exhibit considerable sensorimotor or balance deficits. Type-II vestibular hair cells (VHCs) in Vglut3<sup>+/+</sup> mice were strongly immunoreactive for VGLUT3, while type-I VHCs showed weak immunoreactivity. 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 is sufficient to support vestibular nerve physiology and behavioral function in Vglut3<sup>-/-</sup> mice.
Authors
- Maolei Xiao
- Rebecca P. Seal (ORCID: https://orcid.org/0000-0003-4955-703X)
- Carla M. Yuede (ORCID: https://orcid.org/0000-0001-6362-4767)
- Valentin Militchin
- Susan E. Maloney (ORCID: https://orcid.org/0000-0001-5585-4722)
- Aizhen Yang-Hood
- Mark E. Warchol (ORCID: https://orcid.org/0000-0002-0445-6318)
- Nicholas Rensing
- Mark Allen Rutherford (ORCID: https://orcid.org/0000-0002-2627-6254)
- Tina Pangršič (ORCID: https://orcid.org/0000-0002-7313-1648)
- Ruchi Modgekar
- Zhijun Shen
- Michael Wong
- Suh Jin Lee
- Kevin K. Ohlemiller
- Joseph C. Holt
- Mohona Mukhopadhyay
Institutions
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- Gesellschaft für wissenschaftliche Datenverarbeitung mbH Göttingen (DE)
- Universitätsmedizin Göttingen (DE)
- European Neuroscience Institute Göttingen (DE)
- International Max Planck Research School for Advanced Methods in Process and Systems Engineering (DE)
- University of Rochester (US)
- University of Göttingen (DE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-03-23
- DOI
- https://doi.org/10.1038/s41598-026-43836-7
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 0.00