Abstract
l-glutamate, the neurotransmitter of the majority of excitatory synapses in the brain, acts on three classes of ionotropic receptors: NMDA (N-methyl-d-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptors. Little is known about the physiological role of kainate receptors because in many experimental situations it is not possible to distinguish them from AMPA receptors1,2. Mice with disrupted kainate receptor genes enable the study of the specific role of kainate receptors in synaptic transmission as well as in the neurotoxic effects of kainate. We have now generated mutant mice lacking the kainate-receptor subunit GluR6. The hippocampal neurons in the CA3 region of these mutant mice are much less sensitive to kainate. In addition, a postsynaptic kainate current evoked in CA3 neurons by a train of stimulation of the mossy fibre system is absent in the mutant3,4. We find that GluR6-deficient mice are less susceptible to systemic administration of kainate, as judged by onset of seizures and by the activation of immediate early genes in the hippocampus. Our results indicate that kainate receptors containing the GluR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate.
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Acknowledgements
We thank L. O'Leary, Q.-C. Phan, H. Garjeda, E.Normand and the animal research departments for technical assistance; B. Vissel for help in isolating the genomic clones; M. Iadarola for anti-Fra antibody; M. Allard for help with kainate autoradiography; and Eli Lilly for a gift of GYKI 53655. This work was supported by grants and fellowships from the CNRS, the French MRES, the NIH, the Fondation pour la Recherche Médicale, and the Région Aquitaine (to C.M.), the Schweizerische Nationalfond and the Deutsche Forschungsgemeinschaft (to A.S.), the Spanish MEC (to I.P.-O.), the Conycit-BID (to P.E.C.), a joint program project grant (to F.H.G. and S.F.H.), the NIH (NINDS) and theMcKnight foundation (to S.F.H.).
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Mulle, C., Sailer, A., Pérez-Otaño, I. et al. Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 392, 601–605 (1998). https://doi.org/10.1038/33408
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DOI: https://doi.org/10.1038/33408
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