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Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation.


ABSTRACT: 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.

SUBMITTER: Hoeffer CA 

PROVIDER: S-EPMC3044415 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation.

Hoeffer Charles A CA   Cowansage Kiriana K KK   Arnold Elizabeth C EC   Banko Jessica L JL   Moerke Nathan J NJ   Rodriguez Ricard R   Schmidt Enrico K EK   Klosi Edvin E   Chorev Michael M   Lloyd Richard E RE   Pierre Philippe P   Wagner Gerhard G   LeDoux Joseph E JE   Klann Eric E  

Proceedings of the National Academy of Sciences of the United States of America 20110202 8


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 int  ...[more]

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