Editors' ChoiceTransporters

Hearing About Glutamate Transporters

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Science Signaling  29 Jan 2008:
Vol. 1, Issue 4, pp. ec38
DOI: 10.1126/stke.14ec38

Although three vesicular glutamate transporters (VGLUTs) have been identified, only two are found in identified glutamatergic neurons. In contrast, VGLUT3 is expressed in several populations of neurons that release other classical neurotransmitters, including inhibitory GABAergic interneurons in the hippocampus and cortex, as well as outside the nervous system. Seal et al. found that mice lacking VGLUT3 were profoundly deaf: They failed to show a startle response to loud noises and did not exhibit auditory evoked potentials. Electrophysiological analysis revealed a defect in signaling from the inner hair cells of the cochlea to the auditory nerve, and morphological analysis showed abnormalities of inner hair cell synapses, as well as a moderate loss of cochlear ganglion neurons. Immunofluorescence analysis revealed that VGLUT3 was present in synaptic regions of the inner hair cells of wild-type mice. Furthermore, expression of VGLUT3--but not VGLUT1 or VGLUT2--in the inner hair cells of the rat was confirmed by reverse transcription polymerase chain reaction. Whereas various conductances in the IHCs of the mice lacking VGLUT3 resembled those in wild-type mice, electrophysiological analysis indicated that they failed to release synaptic glutamate. In addition to the defect in the auditory pathway, electroencephalography revealed spontaneous cortical seizures, with little effect on motor activity, in mice lacking VGLUT3. The authors conclude that VGLUT3 is essential for hearing and plays an important role in the regulation of cortical excitability. Ahnert-Hilger and Jahn discuss the work and speculate on the implications of releasing both an excitatory and an inhibitory transmitter from the same neuron.

R. P. Seal, O. Akil, E. Yi, C. M. Weber, L. Grant, J. Yoo, A. Clause, K. Kandler, J. L. Noebels, E. Glowatzki, L. R. Lustig, R. H. Edwards, Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 57, 263-275 (2008). [PubMed]

G. Ahnert-Hilger, R. Jahn, Into great silence without VGLUT3. Neuron 57, 173-174 (2008). [PubMed]

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