Beurrier C, Bonvento G, Kerkerian-Le Goff L, Gubellini P
Institut de Biologie du Développement de Marseille-Luminy, Marseille, France.
Neuroscience. 2009 Feb 18;158(4):1608-15. doi: 10.1016/j.neuroscience.2008.11.018. Epub 2008 Nov 17.
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.
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发挥着重要作用。在这里，我们通过对中等棘状神经元（MSNs）进行体外膜片钳记录，研究了GTs在成年大鼠中调节皮质纹状体谷氨酸能突触传递的作用。GTs的广泛抑制剂dl-苏式-β-苄氧基天冬氨酸（TBOA）增强了兴奋性突触后电流（EPSCs）的电荷转移和衰减时间，但未增强其幅度。此外，TBOA还增强了高频刺激（HFS）方案诱导的电流。有趣的是，当MSNs钳制在+40 mV时，TBOA对EPSCs的作用消失了，在这种情况下，电压依赖性的神经元GTs被阻断。然而，在这种情况下，TBOA仍然能够增强HFS诱导的电流，这表明胶质GTs的作用是在谷氨酸大量释放时调节突触传递。这些数据表明，塑造EPSCs动力学并调节皮质纹状体突触处谷氨酸传递的是神经元GTs，而非胶质GTs。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活动亢进为特征的退行性疾病以及突触可塑性中发挥作用。
