TY - JOUR
T1 - Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice
AU - Mulle, Christophe
AU - Sailer, Andreas
AU - Pérez-Otaño, Isabel
AU - Dickinson-Anson, Heather
AU - Castillo, Pablo E.
AU - Bureau, Ingrid
AU - Maron, Cornelia
AU - Gage, Fred H.
AU - Mann, Jeffrey R.
AU - Bettler, Bernhard
AU - Heinemann, Stephen F.
PY - 1998/4/9
Y1 - 1998/4/9
N2 - 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-5methyl-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 receptors. 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 kainatereceptor subunit GIuR6. 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 mutant. 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 GIuR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate.
AB - 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-5methyl-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 receptors. 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 kainatereceptor subunit GIuR6. 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 mutant. 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 GIuR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate.
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U2 - 10.1038/33408
DO - 10.1038/33408
M3 - Article
C2 - 9580260
AN - SCOPUS:0032499277
SN - 0028-0836
VL - 392
SP - 601
EP - 605
JO - Nature
JF - Nature
IS - 6676
ER -