Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus.
Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus.
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DOI：
10.1523/jneurosci.4845-09.2009
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发表时间：
2009-11-18
期刊：
影响因子：
--
通讯作者：
Diamond JS
中科院分区：
文献类型：
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作者：
Scimemi A;Tian H;Diamond JS
在哺乳动物脑中，兴奋性突触传递的特异性依赖于谷氨酸从活跃突触的快速扩散和星形胶质细胞中谷氨酸转运体的强大摄取能力。神经元谷氨酸转运蛋白在多大程度上影响谷氨酸在细胞外空间（ECS）的寿命仍不清楚。在这里，我们表明，EAAC 1，在海马CA 1区兴奋性突触的主要神经元谷氨酸转运蛋白，缓冲谷氨酸在突触事件和释放的时间过程中，其清除星形胶质细胞。EAAC 1不显著改变突触间隙中受体的激活。相反，它减少了含有NR 2-B-NMDA受体（NR 2B-NMDARs）的突触外/突触外的募集，从而促进了短脉冲高频刺激诱导的长时程增强（LTP）。我们描述了EAAC 1在调节谷氨酸扩散中的新作用，并提出在不同的突触下位置的NMDARs可以对突触强度的调节做出不同的贡献。
In the mammalian brain, the specificity of excitatory synaptic transmission depends on rapid diffusion of glutamate away from active synapses and the powerful uptake capacity of glutamate transporters in astrocytes. The extent to which neuronal glutamate transporters influence the lifetime of glutamate in the extracellular space (ECS) remains unclear. Here we show that EAAC1, the predominant neuronal glutamate transporter at excitatory synapses in hippocampal area CA1, buffers glutamate released during synaptic events and prolongs the time course of its clearance by astrocytes. EAAC1 does not significantly alter activation of receptors in the synaptic cleft. Instead, it reduces recruitment of peri/extrasynaptic NR2-Bcontaining NMDA receptors (NR2B-NMDARs), thereby facilitating induction of long-term potentiation (LTP) by short bursts of high-frequency stimulation. We describe novel roles of EAAC1 in regulating glutamate diffusion and propose that NMDARs at different subsynaptic locations can make distinct contributions to the regulation of synaptic strength.