Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice
Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice
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DOI：
10.1038/33408
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发表时间：
1998-04-09
期刊：
影响因子：
64.8
通讯作者：
Heinemann, SF
中科院分区：
文献类型：
--
作者：
Mulle, C;Sailer, A;Heinemann, SF
l-谷氨酸是大脑中大多数兴奋性突触的神经递质，作用于三类嗜电性受体：NMDA （n -甲基- d -天冬氨酸）、AMPA （α -氨基-3-羟基-5-甲基-4-异唑丙酸）和海因酸盐受体。对盐酸盐受体的生理作用知之甚少，因为在许多实验情况下，不可能将它们与AMPA受体区分开来（1,2）。海因酸盐受体基因被破坏的小鼠能够研究海因酸盐受体在突触传递中的特定作用以及海因酸盐的神经毒性作用。我们现在已经产生了缺乏盐酸盐受体亚基GluR6的突变小鼠。这些突变小鼠的海马神经元CA3区对盐酸盐的敏感性要低得多。此外，由苔藓纤维系统的一系列刺激在CA3神经元中引起的突触后盐酸盐电流在突变体中不存在（3,4）。我们发现，通过癫痫发作和海马体中即时早期基因的激活来判断，glur6缺陷小鼠对海钠酸盐的全身管理不太敏感。我们的研究结果表明，含有GluR6亚基的海盐酸盐受体在突触传递和海盐酸盐的致痫作用中起重要作用。
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 (alpha-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 receptors(1,2). 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 mutant(3,4). 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.