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Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3.

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.

Pubmed ID: 18215623


  • Seal RP
  • Akil O
  • Yi E
  • Weber CM
  • Grant L
  • Yoo J
  • Clause A
  • Kandler K
  • Noebels JL
  • Glowatzki E
  • Lustig LR
  • Edwards RH



Publication Data

January 24, 2008

Associated Grants

  • Agency: NIMH NIH HHS, Id: F32 MH068085
  • Agency: NIDCD NIH HHS, Id: R01 DC004199
  • Agency: NIDCD NIH HHS, Id: R01 DC004199-09
  • Agency: NIDCD NIH HHS, Id: R01 DC004199-10
  • Agency: NIMH NIH HHS, Id: R01 MH050712
  • Agency: NIMH NIH HHS, Id: R01 MH050712-15

Mesh Terms

  • Acoustic Stimulation
  • Amino Acid Transport Systems, Acidic
  • Animals
  • Animals, Newborn
  • Calcium
  • Disease Models, Animal
  • Electric Stimulation
  • Electroencephalography
  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • Hair Cells, Auditory
  • Hearing Loss, Sensorineural
  • Membrane Potentials
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Neurons
  • Quinoxalines
  • Reflex, Startle
  • Seizures
  • Spiral Ganglion