ROLE OF GLUTAMATE TRANSPORTERS IN CORTICOSTRIATAL SYNAPTIC TRANSMISSION
ROLE OF GLUTAMATE TRANSPORTERS IN CORTICOSTRIATAL SYNAPTIC TRANSMISSION
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DOI：
10.1016/j.neuroscience.2008.11.018
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发表时间：
2009-02-18
期刊：
影响因子：
3.3
通讯作者：
Gubellini, P.
中科院分区：
文献类型：
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作者：
Beurrier, C.;Bonvento, G.;Gubellini, P.
高亲和力谷氨酸转运体（GTs）在控制中枢神经系统中这种兴奋性神经递质的细胞外水平方面起主要作用。在此，我们通过对中型多棘神经元（MSNs）进行体外膜片钳记录，对成年大鼠中GTs在调节皮质 - 纹状体谷氨酸能突触传递中的作用进行了研究。兴奋性突触后电流（EPSCs）的电荷转移和衰减时间（而非幅度）被DL - 苏式 - β - 苄氧基天冬氨酸（TBOA，一种广泛的GTs抑制剂）增强。此外，TBOA还增强了高频刺激（HFS）方案所诱导的电流。有趣的是，当MSNs被钳制在 +40 mV时（在此条件下，电压依赖性的神经元GTs被阻断），TBOA对EPSCs的作用消失。然而，在此条件下，TBOA仍然能够增强HFS诱导的电流，这表明当谷氨酸大量释放时，神经胶质GT的作用是调节突触传递。这些数据表明，在皮质 - 纹状体突触处，是神经元GTs而非神经胶质GTs塑造了EPSCs的动力学并调节谷氨酸传递。此外，GTs对突触间隙中谷氨酸浓度的控制可能在许多以皮质 - 纹状体通路过度活跃为特征的退行性疾病以及突触可塑性中起作用。（C）2009国际脑研究组织。由爱思唯尔有限公司出版。保留所有权利。
High-affinity glutamate transporters (GTs) play a major role in controlling the extracellular level of this excitatory neurotransmitter in the CNS. Here we have characterized, by means of in vitro patch-clamp recordings from medium spiny neurons (MSNs), the role of GTs in regulating corticostriatal glutamatergic synaptic transmission in the adult rat. Charge transfer and decay-time, but not amplitude, of excitatory postsynaptic currents (EPSCs) were enhanced by DL-threo-beta-benzyloxyaspartate (TBOA), a broad inhibitor of GTs. Moreover, TBOA also potentiated currents induced by high-frequency stimulation (HFS) protocols. Interestingly, the effect of TBOA on EPSCs was lost when MSNs were clamped at +40 mV, a condition in which neuronal GTs, that are voltage-dependent, are blocked. However, in this condition TBOA was still able to enhance HFS-induced currents, suggesting that glial GT's role is to regulate synaptic transmission when glutamate release is massive. These data suggest that neuronal GTs, rather than glial, shape EPSCs' kinetics and modulate glutamate transmission at corticostriatal synapse. Moreover, the control of glutamate concentration in the synaptic cleft by GTs may play a role in a number of degenerative disorders characterized by the hyperactivity of corticostriatal pathway, as well as in synaptic plasticity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.