Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation
Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation
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DOI：
10.1073/pnas.1013063108
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发表时间：
2011-02-22
影响因子：
11.1
通讯作者：
Klann, Eric
中科院分区：
文献类型：
--
作者：
Hoeffer, Charles A.;Cowansage, Kiriana K.;Klann, Eric
相当多的证据表明，蛋白质合成的全面封锁阻止了长期记忆的初始巩固和postretrieval再巩固。这些发现主要来自于对阻断核糖体功能的药物的研究，从而全面干扰帽依赖性和非依赖性形式的翻译。在这里，我们表明，杏仁核内微量输注4 EGI-1，帽依赖性翻译的小分子抑制剂，选择性地破坏真核起始因子（eIF）4 E和4G之间的相互作用，减弱恐惧记忆巩固，但不巩固。使用行为和生物化学技术相结合，我们提供了在体外和体内的证据表明，eIF 4 E-eIF 4G复合物是更严格地需要由初始学习诱导的可塑性比现有的记忆激活引发。
Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intra-amygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory.