Frey U, Morris R G
Federal Institute for Neurobiology, Gene Regulation and Plasticity, Magdeburg, Germany.
Nature. 1997 Feb 6;385(6616):533-6. doi: 10.1038/385533a0.
Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)-the primary cellular model of memory in the mammalian brain. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation, Because protein synthesis occurs mainly in the cell body, whereas LTP is input-specific, the question arises of how the synapse specificity of late LTP is achieved without elaborate intracellular protein trafficking. We propose that LTP initiates the creation of a short-lasting protein-synthesis-independent 'synaptic tag' at the potentiated synapse which sequesters the relevant protein(s) to establish late LTP. In support of this idea, we now show that weak tetanic stimulation, which ordinarily leads only to early LTP, or repeated tetanization in the presence of protein-synthesis inhibitors, each results in protein-synthesis-dependent late LTP, provided repeated tetanization has already been applied at another input to the same population of neurons. The synaptic tag decays in less than three hours. These findings indicate that the persistence of LTP depends not only on local events during its induction, but also on the prior activity of the neuron.
对海马神经元的反复刺激可诱导突触强度立即且持久地增强，这一现象被称为长时程增强（LTP）——哺乳动物大脑中记忆的主要细胞模型。通过使用转录和翻译抑制剂，可将LTP的早期阶段（持续时间少于三小时）与晚期阶段的LTP区分开来。由于蛋白质合成主要发生在细胞体中，而LTP具有输入特异性，因此就出现了一个问题：在没有复杂的细胞内蛋白质运输的情况下，晚期LTP的突触特异性是如何实现的。我们提出，LTP在增强的突触处启动了一个短暂的、不依赖蛋白质合成的“突触标签”的创建，该标签隔离相关蛋白质以建立晚期LTP。为支持这一观点，我们现在表明，通常仅导致早期LTP的弱强直刺激，或在蛋白质合成抑制剂存在下的反复强直刺激，只要已经在同一群神经元的另一个输入处施加了反复强直刺激，都会导致依赖蛋白质合成的晚期LTP。突触标签在不到三小时内衰减。这些发现表明，LTP的持续性不仅取决于其诱导过程中的局部事件，还取决于神经元先前的活动。
