Role of Glycine Receptors in Glycine-Induced LTD in Hippocampal CA1 Pyramidal Neurons
Role of Glycine Receptors in Glycine-Induced LTD in Hippocampal CA1 Pyramidal Neurons
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DOI：
10.1038/npp.2011.86
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发表时间：
2011-08-01
影响因子：
7.6
通讯作者：
Lu, Wei
中科院分区：
文献类型：
--
作者：
Chen, Rong-Qing;Wang, Shan-Hui;Lu, Wei
海马中的甘氨酸可以通过不同的结合位点对突触NMDA受体（NMDAR）和突触外功能性甘氨酸受体（GlyR）发挥其作用。先前的研究已经报道甘氨酸通过激活突触NMDAR诱导长时程增强（LTP）。然而，很少有人知道的潜在作用的激活GlyRs主要位于突触外区域。我们在这里报告，相对较高水平的甘氨酸实现外源性甘氨酸应用或通过升高内源性甘氨酸积累与甘氨酸转运体的拮抗剂诱导的长期抑郁症（LTD）的兴奋性突触后电流（EPSC）在海马CA 1区锥体神经元。甘氨酸与选择性GlyR拮抗剂士的宁的共同应用改变甘氨酸诱导的LTD（Gly-LTD）为LTP。通过操纵细胞内氯离子浓度来阻断突触后GlyR门控的净氯离子通量未能引起EPSC的任何变化。这些结果表明GlyR参与了Gly-LTD的形成，而且这种化学LTD的形成伴随着突触后AMPA受体的内化，需要NMDAR的激活。因此，我们目前的研究结果揭示了一个重要的功能，GlyR激活和调制门控方向的突触可塑性。Neuropsychopharmacology（2011）36，1948-1958; doi：10.1038/npp.2011.86; 2011年5月18日在线发表
Glycine in the hippocampus can exert its effect on both synaptic NMDA receptors (NMDARs) and extrasynaptic functional glycine receptors (GlyRs) via distinct binding sites. Previous studies have reported that glycine induces long-term potentiation (LTP) through the activation of synaptic NMDARs. However, little is known about the potential role of the activated GlyRs that are largely located in extrasynaptic regions. We report here that relatively high levels of glycine achieved either by exogenous glycine application or by the elevation of endogenous glycine accumulation with an antagonist of the glycine transporter induced long-term depression (LTD) of excitatory postsynaptic currents (EPSCs) in hippocampal CA1 pyramidal neurons. The co-application of glycine with the selective GlyR antagonist strychnine changed glycine-induced LTD (Gly-LTD) to LTP. Blocking the postsynaptic GlyR-gated net chloride flux by manipulating intracellular chloride concentrations failed to elicit any changes in EPSCs. These results suggest that GlyRs are involved in Gly-LTD. Furthermore, this new form of chemical LTD was accompanied by the internalization of postsynaptic AMPA receptors and required the activation of NMDARs. Therefore, our present findings reveal an important function of GlyR activation and modulation in gating the direction of synaptic plasticity. Neuropsychopharmacology (2011) 36, 1948-1958; doi:10.1038/npp.2011.86; published online 18 May 2011