O'Connor J J, Rowan M J, Anwyl R
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.
Nature. 1994 Feb 10;367(6463):557-9. doi: 10.1038/367557a0.
Synaptic transmission mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor plays a key role in a range of plastic processes in the nervous system. These include long-term potentiation of synaptic transmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, neuronal development, excitotoxicity and certain learning tasks. Recently, long-term potentiation of NMDA receptor-mediated synaptic transmission was found to occur following high-frequency (tetanic) stimulation via an unknown mechanism. We show here that activation of metabotropic glutamate (mGlu) receptors by neurally released transmitter underlies this type of long-term potentiation. The whole-cell patch-clamp technique in the 'thick' slice of the rat dentate gyrus was used to measure NMDA receptor-mediated excitatory postsynaptic currents. We have found that mGlu receptor activation by a selective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA currents. Moreover, both forms of potentiation were greatly reduced by the mGlu receptor antagonists L-2-amino-3-phosphonopropionate and (R,S)-alpha-methyl-4-carboxyphenylglycine.
由N-甲基-D-天冬氨酸（NMDA）谷氨酸受体介导的突触传递在神经系统的一系列可塑性过程中起关键作用。这些过程包括由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导的突触传递的长期增强、神经元发育、兴奋性毒性和某些学习任务。最近，发现通过高频（强直）刺激后，NMDA受体介导的突触传递会通过未知机制发生长期增强。我们在此表明，神经释放的递质对代谢型谷氨酸（mGlu）受体的激活是这种长期增强的基础。在大鼠齿状回的“厚”切片中使用全细胞膜片钳技术来测量NMDA受体介导的兴奋性突触后电流。我们发现，选择性激动剂对mGlu受体的激活产生了一种持久的增强，这种增强与这些NMDA电流的长期增强相互排斥。此外，mGlu受体拮抗剂L-2-氨基-3-膦丙酸和（R,S）-α-甲基-4-羧基苯甘氨酸大大降低了这两种增强形式。
