MRC Centre for Synaptic Plasticity, School of Physiology & Pharmacology, University of Bristol, BS8 1TD, UK.
Neurochem Int. 2012 Sep;61(4):482-9. doi: 10.1016/j.neuint.2012.04.021. Epub 2012 Apr 27.
Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre - CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/Glu(K5))-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/Glu(K6)). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre - CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection.
长时程增强（LTP）是一种成熟的实验模型，用于研究学习和记忆的突触基础。海马苔藓纤维-CA3 突触的 LTP 不同寻常，因为它通常不依赖 N-甲基-D-天冬氨酸（NMDA）受体。相反，触发苔藓纤维 LTP 的似乎是 kainate 受体（KARs）。尽管普遍认为，突触前 KARs 在频率易化和 LTP 中发挥重要作用，但它们的亚基组成仍然存在很大争议。我们之前报道过，选择性拮抗 GluK1（以前称为 GluR5/Glu(K5)）-KAR 可以阻断频率易化和 LTP，但其他组未能复制这种效应。此外，受体敲除和 mRNA 表达研究的数据反对 GluK1 的主要作用，支持 GluK2（以前称为 GluR6/Glu(K6)）的更中心作用。药理学实验争议的潜在原因可能在于使用的制剂不同。在这里，我们表明，在苔藓纤维-CA3 突触的突触可塑性的药理学敏感性存在差异，这取决于切片方向。在横切片中，fEPSP 的 LTP 始终对 GluK1 选择性拮抗剂有抗性，而在矢状切片中，LTP 始终被 GluK1 选择性拮抗剂阻断。此外，频率易化的幅度和对 mGlu2/3 受体激动剂 DCG-IV 的敏感性存在明显差异。使用颗粒细胞的顺行标记，我们表明，两种方向的切片都具有完整的苔藓纤维和大、小的突触前末梢。横切片具有更密集的纤维束，但较小比例的巨大苔藓纤维末梢。这些结果进一步证明了苔藓纤维投射的功能特性具有相当大的异质性。
