Bortolotto Z A, Bashir Z I, Davies C H, Taira T, Kaila K, Collingridge G L
Department of Pharmacology, University of Birmingham Medical School, UK.
J Neurosci Methods. 1995 Jun;59(1):19-24. doi: 10.1016/0165-0270(94)00189-n.
There has been considerable interest recently in trying to elucidate the roles of metabotropic glutamate receptors (mGluRs) in the induction of long-term potentiation (LTP) in area CA1 of rat hippocampal slices. This has come about principally because of the development of specific mGluR agonists and antagonists. Recently we reported that the competitive mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks the induction of LTP but not short-term potentiation (STP). We describe here the dose-dependency of the MCPG block; there is no effect at 100 microM while at 200 microM the block of LTP is normally complete but STP is spared. A higher concentration of MCPG (500 microM) has the same effect as 200 microM. We have also reported recently that high-frequency (tetanic) stimulation conditions a pathway such that MCPG fails to block the induction of subsequent LTP. We illustrate here that the conditioning effect of a tetanus lasts at least 6 h. We show how the pathway can be conditioned, without any persistent change in the synaptic response, by delivering tetanic stimulation in the presence of the specific NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (AP5). The pathway can subsequently be deconditioned by delivering low-frequency stimulation (900 shocks at 2 Hz) so that MCPG blocks the induction of subsequent LTP. We also have reported that the specific mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylate (ACPD) can induce LTP without the need for STP.(ABSTRACT TRUNCATED AT 250 WORDS)
最近，人们对阐明代谢型谷氨酸受体（mGluRs）在大鼠海马切片CA1区长期增强（LTP）诱导中的作用产生了浓厚兴趣。这主要是由于特异性mGluR激动剂和拮抗剂的开发。最近我们报道，竞争性mGluR拮抗剂（+）-α-甲基-4-羧基苯甘氨酸（MCPG）可阻断LTP的诱导，但不影响短期增强（STP）。我们在此描述MCPG阻断的剂量依赖性；100微摩尔时无作用，而在200微摩尔时LTP的阻断通常是完全的，但STP不受影响。更高浓度的MCPG（500微摩尔）与200微摩尔具有相同的效果。我们最近还报道，高频（强直）刺激可对一条通路进行条件化，使得MCPG无法阻断后续LTP的诱导。我们在此说明强直刺激的条件化作用至少持续6小时。我们展示了在特异性NMDA受体拮抗剂D-2-氨基-5-膦酰戊酸（AP5）存在下通过给予强直刺激，如何在突触反应无任何持续变化的情况下对该通路进行条件化。随后可通过给予低频刺激（2赫兹下900次电击）使该通路去条件化，从而使MCPG阻断后续LTP的诱导。我们还报道，特异性mGluR激动剂1-氨基环戊烷-（1S，3R）-二羧酸（ACPD）可在无需STP的情况下诱导LTP。（摘要截短于250字）
