Grover L M, Yan C
Department of Physiology, Marshall University School of Medicine, Huntington, West Virginia 25755-9340, USA.
J Neurophysiol. 1999 Dec;82(6):2956-69. doi: 10.1152/jn.1999.82.6.2956.
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), GDPbetaS]. Although loading postsynaptic CA1 pyramidal neurons with GDPbetaS significantly reduced G-protein dependent postsynaptic potentials, GDPbetaS 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 field 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 mGluRs 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.
先前的研究表明，代谢型谷氨酸受体（mGluRs）参与大鼠海马体CA1区不依赖N-甲基-D-天冬氨酸（NMDA）受体的长时程增强（LTP）。为了更深入了解mGluRs在不依赖NMDA受体的LTP中所起的具体作用，我们采用全细胞记录法，用一种G蛋白抑制剂[鸟苷-5'-O-(2-硫代二磷酸)，GDPβS]将单个CA1锥体神经元进行负载。尽管用GDPβS负载突触后CA1锥体神经元显著降低了G蛋白依赖性突触后电位，但GDPβS未能阻止不依赖NMDA受体的LTP，这表明突触后G蛋白依赖性mGluRs并非必需。我们还进行了一系列细胞外场电位实验，应用了组选择性mGluR拮抗剂。我们之前已确定，在不依赖NMDA受体的LTP的最初30 - 45分钟内，配对脉冲易化（PPF）降低。为了确定mGluRs是否可能参与这些PPF变化，我们在细胞外场电位实验中采用双脉冲刺激方案来测量PPF。不依赖NMDA受体的LTP被II组mGluR拮抗剂[(2S)-α-乙基谷氨酸]和III组mGluR拮抗剂[(RS)-α-环丙基-4-膦酰基苯甘氨酸]所阻断，但未被其他II组和III组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]所阻断。我们所检测的I组mGluR拮抗剂[(RS)-1-氨基茚满-1,5-二羧酸和7-(羟基亚氨基)环丙烷[b]色烯-1a-羧酸乙酯]均未阻断不依赖NMDA受体的LTP。即使LTP本身被阻断，我们所检测的任何组选择性mGluR拮抗剂均未阻止伴随不依赖NMDA受体的LTP的PPF变化。最后，我们发现，在III组mGluR拮抗剂存在的情况下进行强直刺激会导致对照（未强直刺激）输入通路出现非特异性增强。综合来看，我们的结果表明突触后I组mGluRs不参与不依赖NMDA受体的LTP。II组和/或III组mGluRs是必需的，但这些mGluRs在不依赖NMDA受体的LTP中所起作用的具体细节尚不确定。基于我们所获得的结果模式，我们认为II组mGluRs是诱导不依赖NMDA受体的LTP所必需的，并且III组mGluRs通过抑制附近未强直刺激突触的增强来参与确定不依赖NMDA受体的LTP的输入特异性。
