ALTERED SYNAPTIC PHYSIOLOGY AND REDUCED SUSCEPTIBILITY TO KAINATE-INDUCED SEIZURES IN GLUR6-DEFICIENT MICE

L-glutamate, the neurotransmitter of the majority of excitatory synaps es in the brain, acts on three classes of ionotropic receptors: NMDA ( N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazol e propionic acid) and kainate receptors. Little is known about the phy siological role of kainate receptors because in many experimental situ ations it is not possible to distinguish them from AMPA receptors(1,2) . Mice with disrupted kainate receptor genes enable the study of the s pecific role of kainate receptors in synaptic transmission as well as in the neurotoxic effects of kainate. We have now generated mutant mic e lacking the kainate-receptor subunit GluR6. The hippocampal neurons in the CA3 region of these mutant mice are much less sensitive to kain ate. 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(3,4). We find that GluR6-deficient mice are less susceptible to systemic administration of kainate, as judged by onset of seizures an d by the activation of immediate early genes in the hippocampus. Our r esults indicate that kainate receptors containing the GluR6 subunit ar e important in synaptic transmission as well as in the epileptogenic e ffects of kainate.