Xiao M Y, Niu Y P, Wigstrom H
Department of Medical Biophysics, Goteborg University, Sweden.
Synapse. 1997 Aug;26(4):329-40. doi: 10.1002/(SICI)1098-2396(199708)26:4<329::AID-SYN1>3.0.CO;2-8.
Field excitatory postsynaptic potentials (EPSPs) were recorded in the CA1 region of hippocampal slices from 12-18-day-old rats. The isolated N-methyl-D-aspartate (NMDA) receptor mediated field EPSP as well as the composite field EPSP of both NMDA and alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor mediated components were obtained in low Mg2+ solutions with 10 microM or 1 microM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. The isolated AMPA receptor mediated field EPSP was obtained either in normal Mg2+ solution or in a low Mg2+ solution in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid. The waveforms of the field EPSPs were studied and the effect of long-term depression (LTD) on these waveforms was compared with the effects of several pharmacological agents that attenuate the synaptic efficacy. It was shown that LTD occurred without changes in the waveforms of isolated AMPA and NMDA EPSPs. Reducing the number of release sites by lowering the stimulus strength or reducing the probability of transmitter release by an adenosine agonist N6-cyclohexyl-adenosine both mimicked the LTD-induced changes. Partial blockade of the AMPA receptors was also without effect on the waveforms of isolated AMPA EPSPs. In contrast, partial blockade of the NMDA receptors in several different ways resulted in waveform changes. A similar result could be inferred from experiments using composite field EPSPs. The synaptic attenuation caused by a partial blockade of NMDA receptors therefore appears to differ mechanistically from that involved in LTD, arguing against a postsynaptic locus of the modification involved in LTD. However, directly testing for alterations in transmitter release using the open channel blocker of NMDA receptors MK-801 failed in revealing such presynaptic changes during LTD. Our results therefore suggest that LTD might be due to a coordinated pre- and postsynaptic change instead of distinct pre- or postsynaptic modifications.
在12至18日龄大鼠的海马切片CA1区记录场兴奋性突触后电位（EPSP）。在分别含有10微摩尔或1微摩尔AMPA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）的低镁溶液中，获得分离的N-甲基-D-天冬氨酸（NMDA）受体介导的场EPSP以及NMDA和α-氨基-3-羟基-5-甲基异恶唑丙酸（AMPA）受体介导成分的复合场EPSP。分离的AMPA受体介导的场EPSP在正常镁溶液中或在存在NMDA受体拮抗剂D-2-氨基-5-磷酸戊酸的低镁溶液中获得。研究了场EPSP的波形，并将长期抑制（LTD）对这些波形的影响与几种减弱突触效能的药理剂的影响进行了比较。结果表明，LTD发生时，分离的AMPA和NMDA EPSP的波形没有变化。通过降低刺激强度减少释放位点数量或通过腺苷激动剂N6-环己基腺苷降低递质释放概率，两者都模拟了LTD诱导的变化。AMPA受体的部分阻断对分离的AMPA EPSP的波形也没有影响。相反，以几种不同方式对NMDA受体进行部分阻断会导致波形变化。从使用复合场EPSP的实验中可以推断出类似的结果。因此，NMDA受体部分阻断引起的突触减弱在机制上似乎与LTD所涉及的不同，这与LTD所涉及的修饰的突触后位点相矛盾。然而，使用NMDA受体开放通道阻断剂MK-801直接测试递质释放的变化，未能揭示LTD期间这种突触前变化。因此，我们的结果表明，LTD可能是由于突触前和突触后协调变化，而不是明显的突触前或突触后修饰。
