Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2-/- mice
Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2-/- mice
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DOI：
10.1523/jneurosci.23-02-00422.2003
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发表时间：
2003-01-15
影响因子：
5.3
通讯作者：
Heinemann, SF
中科院分区：
文献类型：
--
作者：
Contractor, A;Sailer, AW;Heinemann, SF
红藻氨酸（KA）受体亚基的多聚体组装形成谷氨酸门控离子通道，其介导EPSC并在某些中枢突触处作为神经递质释放的突触前调节剂发挥作用。KA 2亚基是许多神经元红藻氨酸受体的可能成分，因为它在CNS中的大多数神经元中广泛表达。我们已经研究了这种受体亚基的遗传消融在海马切片，红藻氨酸受体定位于突触前和突触后位点的苔藓纤维-CA 3锥体细胞突触的突触传递的影响。我们发现在KA 2（-/-）小鼠的神经元中，突触后和突触前苔藓纤维红藻氨酸受体的功能都发生了改变。调节苔藓纤维末梢谷氨酸释放的突触前易化性自身受体对外源性激动剂和突触谷氨酸的亲和力降低。虽然在KA 2（-/-）神经元的苔藓纤维突触中，由同型突触谷氨酸释放引起的突触前易化是正常的，但不存在由谷氨酸从CA 3侧支突触溢出引起的异突触红藻氨酸受体介导的易化。与受体的谷氨酸亲和力降低一致，在敲除小鼠中，突触后红藻氨酸介导的EPSC的半衰期较短。这些结果确定了KA 2亚基作为在突触前和突触后苔藓纤维红藻氨酸受体上红藻氨酸受体功能的决定因素。
Multimeric assemblies of kainate (KA) receptor subunits form glutamate-gated ion channels that mediate EPSCs and function as presynaptic modulators of neurotransmitter release at some central synapses. The KA2 subunit is a likely constituent of many neuronal kainate receptors, because it is widely expressed in most neurons in the CNS. We have studied the effect of genetic ablation of this receptor subunit on synaptic transmission at the mossy-fiber-CA3 pyramidal cell synapse in hippocampal slices, where kainate receptors are localized to both presynaptic and postsynaptic sites. We found that both postsynaptic and presynaptic mossy- fiber kainate receptor function is altered in neurons from KA2(-/-) mice. The presynaptic facilitatory autoreceptor, which modulates glutamate release from mossy- fiber terminals, had a reduced affinity for exogenous agonists and synaptic glutamate. Although presynaptic facilitation attributable to homosynaptic glutamate release was normal at mossy- fiber synapses in KA2(-/-) neurons, heterosynaptic kainate receptor-mediated facilitation resulting from the spillover of glutamate from CA3 collateral synapses was absent. Consistent with a decrease in glutamate affinity of the receptor, the half-decay of the postsynaptic kainate-mediated EPSC was shorter in the knock-out mice. These results identify the KA2 subunit as a determinant of kainate receptor function at presynaptic and postsynaptic mossy- fiber kainate receptors.