title: Glutamate co-release at GABA/glycinergic synapses is crucial for the refinement of an inhibitory map.
abstract: Many nonglutamatergic synaptic terminals in the mammalian brain contain the vesicular glutamate transporter 3 (VGLUT3), indicating that they co-release the excitatory neurotransmitter glutamate. However, the functional role of glutamate co-transmission at these synapses is poorly understood. In the auditory system, VGLUT3 expression and glutamate co-transmission are prominent in a developing GABA/glycinergic sound-localization pathway. We found that mice with a genetic deletion of Vglut3 (also known as Slc17a8) had disrupted glutamate co-transmission and severe impairment in the refinement of this inhibitory pathway. Specifically, loss of glutamate co-transmission disrupted synaptic silencing and the strengthening of GABA/glycinergic connections that normally occur with maturation. Functional mapping studies further revealed that these deficits markedly degraded the precision of tonotopy in this inhibitory auditory pathway. These results indicate that glutamate co-transmission is crucial for the synaptic reorganization and topographic specification of a developing inhibitory circuit.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Eye and Ear Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Noh
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Seal
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Garver
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Karl
authors.initials: K
authors.lastname: Kandler
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001306:Auditory Pathways / Q000254:growth & development / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D017626:Cochlear Nucleus / Q000254:growth & development / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009847:Olivary Nucleus / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D018698:Glutamic Acid; D005998:Glycine; D008565:Membrane Proteins; D005680:gamma-Aminobutyric Acid; C516233:otoferlin protein, mouse; C504941:Slc17a8 protein, mouse