Blockade of glutamate transporters facilitates cerebellar synaptic long-term depression

Blockade of glutamate transporters facilitates cerebellar synaptic long-term depression
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谷氨酸转运蛋白的阻断促进小脑突触长期抑制

DOI:
10.1097/wnr.0b013e328328f397
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发表时间:
2009-03
期刊:
影响因子:
1.7
通讯作者:
Su LD
Su LD
中科院分区:
医学4区
文献类型:
--
作者:
Shen Y;Su LD

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兴奋性氨基酸转运蛋白(EAAT)被认为是限制细胞外谷氨酸浓度的具体作用知之甚少。在小脑攀爬纤维-浦肯野细胞突触,EAAT 4和代谢型谷氨酸受体1(mGluR 1)密切表达在周围的突触后位置,表明EAAT 4可能调节mGluR 1的激活。我们通过应用谷氨酸转运体阻断剂DL-苏型-苄氧基天冬氨酸和D-天冬氨酸研究了EAAT 4对突触可塑性的作用。抑制EAAT 4显著延长刺激攀爬纤维引起的AMPA受体介导的兴奋性突触后电流。损害谷氨酸摄取促进mGluR 1依赖的攀爬纤维浦肯野细胞突触长期抑制(LTD)。谷氨酸摄取阻滞剂也足以拯救攀登纤维浦肯野细胞突触LTD,未能引起较弱的破伤风。我们的研究结果表明,神经元谷氨酸转运蛋白强烈影响mGluR 1依赖性小脑LTD。
Excitatory amino acid transporters (EAATs) are believed to limit extracellular glutamate concentrations with specific roles poorly understood. At cerebellar climbing fiber-Purkinje cell synapse, EAAT4 and metabotropic glutamate receptor 1 (mGluR1) are closely expressed in surrounding postsynaptic locations, suggesting that EAAT4 may regulate mGluR1 activation. We examined the actions of EAAT4 on synaptic plasticity by applying blockers of glutamate transporters, DL-threo-&bgr;-benzyloxyaspartic acid and D-aspartate. Inhibition of EAAT4 markedly prolonged AMPA receptor-mediated excitatory postsynaptic currents evoked by stimulating climbing fibers. Impairing glutamate uptake facilitated mGluR1-dependent climbing fiber-Purkinje cell synaptic long-term depression (LTD). Glutamate uptake blockers also sufficiently rescued climbing fiber-Purkinje cell synaptic LTD that failed to be induced by a weaker tetanus. Our results suggest that neuronal glutamate transporters strongly influence mGluR1-dependent cerebellar LTD.
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