Kelly A, Mullany P M, Lynch M A
Department of Physiology, Trinity College, Dublin, Ireland.
Hippocampus. 2000;10(4):431-7. doi: 10.1002/1098-1063(2000)10:4<431::AID-HIPO9>3.0.CO;2-Z.
Despite the concentration of effort in recent years, the mechanisms underlying the expression of long-term potentiation (LTP) in the hippocampus remain elusive, but amidst the uncertainty and sometimes controversy, one consistent finding is emerging; this is that late-phase LTP requires synthesis of proteins. This hypothesis was first proposed by a number of groups who reported that the more persistent components of LTP were blocked by protein synthesis inhibitors, and was supported by a significant literature which indicated that morphological changes accompanied LTP. Recent evidence indicated that the increase in protein synthesis may be cAMP-dependent and that subsequent activation of the transcription factor, CREB, represented one step in the cascade of events leading to protein synthesis. Whether protein synthesis occurs in presynaptic or postsynaptic neurons, or both, is still a subject of debate. Here we present evidence which suggests that LTP in perforant path-granule cell synapses is accompanied by protein synthesis, specifically synthesis of synaptic vesicle proteins, in the entorhinal cortex. We also show that protein synthesis is decreased in the entorhinal cortex of aged rats and a strain of rat which is genetically hypertensive, both of which exhibited impaired LTP. We propose that that the observed increase in protein synthesis in the entorhinal cortex, which accompanied LTP in the dentate gyrus, contributes to the reported changes in morphology in the presynaptic terminal.
尽管近年来人们集中精力进行研究，但海马体中长时程增强（LTP）表达的潜在机制仍然难以捉摸。不过，在种种不确定性以及有时存在的争议之中，一个一致的发现正在浮现，即晚期LTP需要蛋白质合成。这一假说最初由多个研究小组提出，他们报告称LTP中更持久的成分会被蛋白质合成抑制剂阻断，并且有大量文献支持这一观点，这些文献表明LTP伴随着形态学变化。最近的证据表明，蛋白质合成的增加可能依赖于环磷酸腺苷（cAMP），并且转录因子CREB的后续激活代表了导致蛋白质合成的一系列事件中的一个步骤。蛋白质合成是发生在突触前神经元还是突触后神经元，或者两者都发生，仍然是一个有争议的话题。在这里，我们提供的证据表明，内嗅皮质中穿通通路-颗粒细胞突触的LTP伴随着蛋白质合成，特别是突触小泡蛋白的合成。我们还表明，老年大鼠和一种遗传性高血压大鼠品系的内嗅皮质中蛋白质合成减少，这两种大鼠均表现出LTP受损。我们提出，在内嗅皮质中观察到的伴随齿状回LTP的蛋白质合成增加，促成了突触前终末中报道的形态学变化。
