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蛋白质合成是突触对抗长时程增强减弱的免疫所必需的。

Protein synthesis is required for synaptic immunity to depotentiation.

作者信息

Woo Newton H, Nguyen Peter V

机构信息

Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada.

出版信息

J Neurosci. 2003 Feb 15;23(4):1125-32. doi: 10.1523/JNEUROSCI.23-04-01125.2003.

DOI:10.1523/JNEUROSCI.23-04-01125.2003
PMID:12598600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6742257/
Abstract

De novo protein synthesis and transcription are necessary for the expression of long-lasting synaptic potentiation [long-term potentiation (LTP)] in hippocampal area CA1 and for the consolidation of long-term memory. The stability of LTP and its longevity require macromolecular synthesis at later stages, but a specific role for early protein synthesis has not been identified. Using electrophysiological recording methods in mouse hippocampal slices, we show that multiple trains of high-frequency stimulation provide immediate synaptic immunity to depotentiation. This immunity to depotentiation is dependent on the amount of synaptic stimulation used to induce LTP, it is input specific, and it is prevented by inhibitors of protein synthesis. We propose that local translation mediates input-specific synaptic immunity against depotentiation. We also present evidence suggesting that, in addition to translation, products of transcription can provide cell-wide immunity to depotentiation via heterosynaptic transfer of synaptic immunity between distinct pathways in area CA1. Protein synthesis and transcription may importantly regulate long-term storage of information by conferring synaptic immunity to depotentiation at previously potentiated synapses.

摘要

从头合成蛋白质和转录对于海马体CA1区持久的突触增强[长期增强(LTP)]的表达以及长期记忆的巩固是必要的。LTP的稳定性及其持久性在后期需要大分子合成,但早期蛋白质合成的具体作用尚未明确。通过在小鼠海马体切片中使用电生理记录方法,我们发现多串高频刺激可立即为去增强提供突触免疫。这种对去增强的免疫取决于用于诱导LTP的突触刺激量,具有输入特异性,并且会被蛋白质合成抑制剂阻断。我们提出局部翻译介导针对去增强的输入特异性突触免疫。我们还提供了证据表明,除了翻译之外,转录产物可以通过CA1区不同通路之间突触免疫的异突触转移为去增强提供全细胞免疫。蛋白质合成和转录可能通过赋予先前增强的突触对去增强的突触免疫来重要地调节信息的长期存储。

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本文引用的文献

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Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation.钙/钙调蛋白依赖性蛋白激酶IIα(CaMKIIα)树突翻译的破坏会损害突触可塑性的稳定和记忆巩固。
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Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training.间隔训练增强长时程增强效应和长期记忆需要蛋白质合成。
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Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture.组成型活性CREB蛋白的表达通过增强突触捕获促进长时程增强的晚期阶段。
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Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis.脑源性神经营养因子在成年完整海马体中诱导长时程增强:需要与CREB偶联的ERK激活以及Arc合成上调。
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A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation.一种高效的蛋白质转导系统,揭示了蛋白激酶A在持久的长期增强效应中的作用。
J Neurosci. 2001 Aug 15;21(16):6000-7. doi: 10.1523/JNEUROSCI.21-16-06000.2001.