Abstract
The expression of unconventional vesicular glutamate transporter VGLUT3 by neurons known to release a different classical transmitter has suggested novel roles for signaling by glutamate, but this distribution has raised questions about whether the protein actually contributes to glutamate release. We now report that mice lacking VGLUT3 are profoundly deaf due to the absence of glutamate release from hair cells at the first synapse in the auditory pathway. The early degeneration of some cochlear ganglion neurons in knockout mice also indicates an important developmental role for the glutamate released by hair cells before the onset of hearing. In addition, the mice exhibit primary, generalized epilepsy that is accompanied by remarkably little change in ongoing motor behavior. The glutamate release conferred by expression of VGLUT3 thus has an essential role in both function and development of the auditory pathway, as well as in the control of cortical excitability.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acoustic Stimulation / methods
-
Amino Acid Transport Systems, Acidic / deficiency*
-
Animals
-
Animals, Newborn
-
Calcium / metabolism
-
Disease Models, Animal
-
Electric Stimulation / methods
-
Electroencephalography / methods
-
Excitatory Amino Acid Antagonists / pharmacology
-
Glutamic Acid / metabolism
-
Hair Cells, Auditory / metabolism
-
Hearing Loss, Sensorineural / etiology
-
Hearing Loss, Sensorineural / genetics*
-
Hearing Loss, Sensorineural / pathology
-
Membrane Potentials / drug effects
-
Membrane Potentials / physiology
-
Membrane Potentials / radiation effects
-
Membrane Proteins / metabolism
-
Mice
-
Mice, Knockout
-
Microscopy, Electron, Transmission / methods
-
Neurons / pathology
-
Neurons / ultrastructure
-
Quinoxalines / pharmacology
-
Reflex, Startle / physiology
-
Seizures / etiology
-
Seizures / genetics*
-
Spiral Ganglion / pathology
Substances
-
Amino Acid Transport Systems, Acidic
-
Excitatory Amino Acid Antagonists
-
Membrane Proteins
-
Quinoxalines
-
otoferlin protein, mouse
-
vesicular glutamate transporter 3, mouse
-
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
-
Glutamic Acid
-
Calcium