{"doi":"10.1101/2025.10.15.682551","title":"Persistence of vestibular function in the absence of glutamatergic transmission from hair cells","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":578130,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1488181,"name":"Ruchi Modgekar","orcid":null,"position":1,"is_corresponding":false},{"id":1488182,"name":"Aizhen Yang-Hood","orcid":null,"position":2,"is_corresponding":false},{"id":662707,"name":"Kevin K. Ohlemiller","orcid":null,"position":3,"is_corresponding":false},{"id":507563,"name":"Valentin Militchin","orcid":null,"position":4,"is_corresponding":false},{"id":645356,"name":"Maolei Xiao","orcid":null,"position":5,"is_corresponding":false},{"id":776763,"name":"Zhijun Shen","orcid":null,"position":6,"is_corresponding":false},{"id":480211,"name":"Nicholas Rensing","orcid":null,"position":7,"is_corresponding":false},{"id":479506,"name":"Michael Wong","orcid":"0000-0002-3796-743X","position":8,"is_corresponding":false},{"id":247858,"name":"Suhjin Lee","orcid":"0000-0002-9943-9253","position":9,"is_corresponding":false},{"id":247861,"name":"Rebecca P. Seal","orcid":"0000-0003-4955-703X","position":10,"is_corresponding":false},{"id":356626,"name":"Mark E. Warchol","orcid":"0000-0002-0445-6318","position":11,"is_corresponding":false},{"id":366327,"name":"Susan E. Maloney","orcid":"0000-0001-5585-4722","position":12,"is_corresponding":false},{"id":225564,"name":"Carla M. Yuede","orcid":"0000-0001-6362-4767","position":13,"is_corresponding":false},{"id":371025,"name":"Mark A. Rutherford","orcid":"0000-0002-2627-6254","position":14,"is_corresponding":false},{"id":1487807,"name":"Tina Pangršič","orcid":"0000-0002-7313-1648","position":15,"is_corresponding":false},{"id":1488180,"name":"Mohona Mukhopadhyay","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:58:20.638044Z","pmid":"41279968","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}