Evidence for involvement of group II/III metabotropic glutamate receptors in NMDA receptor-independent long-term potentiation in area CA1 of rat hippocampus
Evidence for involvement of group II/III metabotropic glutamate receptors in NMDA receptor-independent long-term potentiation in area CA1 of rat hippocampus
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DOI：
10.1152/jn.1999.82.6.2956
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发表时间：
1999-12-01
影响因子：
2.5
通讯作者：
Yan, C
中科院分区：
文献类型：
--
作者：
Grover, LM;Yan, C
II/III组代谢性谷氨酸受体参与大鼠海马CAL区NMDA受体非依赖性长时程增强的证据。J.神经生理素。82：2956-2969,1999。以往的研究表明，代谢性谷氨酸受体(MGluRs)参与了大鼠海马区CA1区N-甲基-D-天冬氨酸(NMDA)受体非依赖性长时程增强(LTP)。为了进一步了解mGluRs在N-甲基-D-天冬氨酸受体非依赖性长时程增强中的具体作用，我们采用全细胞记录的方法，在单个CA1区锥体神经元中加入G蛋白抑制剂[鸟苷-5‘-O-(2-硫代二磷酸)，国内生产总值βS]。尽管向突触后CA1区锥体神经元注入GDPβS显著降低了G蛋白依赖的突触后电位，但GDPβS未能阻止NMDA型受体非依赖的LTP，提示突触后G蛋白依赖的mGluR不是必需的。我们还进行了一系列胞外场电位实验，其中我们应用了基团选择性mGluR拮抗剂。我们先前已经确定，在NMDA受体非依赖性LTP的前30-45分钟，成对脉冲促进(PPF)减少。为了确定mGluRs是否可能参与这些PPF的变化，我们使用双脉冲刺激方案在保持电位的实验中测量PPF。NMDA型受体非依赖性长时程增强可被一种II型mGluR拮抗剂[(2S)-α-乙基谷氨酸]和一种III型mGluR拮抗剂[(RS)-alpha-cyclopropyl-4-phosphonophenylglycine]，所阻断，而其他两种mGluR拮抗剂[(RS)-α-甲基丝氨酸-O-磷酸单苯酯或(RS)-α-甲基丝氨酸-O-磷酸]不能阻止这种非受体依赖性长时程增强。(RS)-1-氨基-1，5-二羧酸和7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate乙酯均不能阻止NMDA型受体非依赖性长时程增强。我们检查的任何组选择性mGluR拮抗剂都不能阻止伴随NMDA受体非依赖性LTP的PPF变化，即使LTP本身被阻断。最后，我们发现，在存在III型mGluR拮抗剂的情况下，强直刺激导致对照(非强直)输入通路的非特异性增强。综上所述，我们的结果反对突触后I组mGluRs参与NMDA受体非依赖性LTP。第二组和/或第三组mCluRs是必需的，但这些mGluR在NMDA受体非依赖性LTP中所起作用的具体细节尚不确定。根据我们得到的结果，我们认为II组mGluRs是诱导NMDA受体非依赖性LTP所必需的，而III组mGluRs通过抑制附近非强直突触的增强来决定NMDA受体非依赖性LTP的输入特异性。
Evidence for involvement of group II/III metabotropic glutamate receptors in NMDA receptor-independent long-term potentiation in area CAL of rat hippocampus. J. Neurophysiol. 82: 2956-2969, 1999. Previous studies implicated metabotropic glutamate receptors (mGluRs) in N-methyl-D-aspartate (NMDA) receptor-independent long-term potentiation (LTP) in area CA1 of the rat hippocampus. To learn more about the specific roles played by mGluRs in NMDA receptor-independent LTP, we used whole cell recordings to load individual CA1 pyramidal neurons with a G-protein inhibitor [guanosine-5' -O-(2-thiodiphosphate), GDP beta S]. Although loading postsynaptic CA1 pyramidal neurons with GDP beta S significantly reduced G-protein dependent postsynaptic potentials, GDP beta S failed to prevent NMDA receptor- independent LTP, suggesting that postsynaptic G-protein-dependent mGluRs are not required. We also performed a series of extracellular field potential experiments in which we applied group-selective mGluR antagonists. We had previously determined that paired-pulse facilitation (PPF) was decreased during the first 30 -45 min of NMDA receptor-independent LTP. To determine if mGluRs might be involved in these PPF changes, we used a twin-pulse stimulation protocol to measure PPF in held potential experiments. NMDA receptor-independent LTP was prevented by a group II mGluR antagonist [(2S)-alpha-ethylglutamic acid] and a group III mGluR antagonist [(RS)-alpha-cyclopropyl-4-phosphonophenylglycine], but was not prevented by other group II and III mGluR antagonists [(RS) -alpha-methylserine-O-phosphate monophenyl ester or (RS)-alpha-methylserine-O-phosphate]. NMDA receptor-independent LTP was not prevented by either of the group I mGluR antagonists we examined, (RS)-1-aminoindan-1,5-dicarboxylic acid and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. The PPF changes which accompany NMDA receptor-independent LTP were not prevented by any of the group-selective mGluR antagonists we examined, even when the LTP itself was blocked. Finally, we found that tetanic stimulation in the presence of group III mGluR antagonists lead to nonspecific potentiation in control (nontetanized) input pathways. Taken together, our results argue against the involvement of postsynaptic group I mGluRs in NMDA receptor-independent LTP. Group II and/or group III mcluRs are required, but the specific details of the roles played by these mGluRs in NMDA receptor-independent LTP are uncertain. Based on the pattern of results we obtained, we suggest that group II mGluRs are required for induction of NMDA receptor-independent LTP, and that group III mGluRs are involved in determining the input specificity of NMDA receptor-independent LTP by suppressing potentiation of nearby, nontetanized synapses.