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

Charles A. Hoeffer, Kiriana K. Cowansage, Elizabeth C. Arnold, Jessica L. Banko, Nathan J. Moerke, Ricard Rodriguez, Enrico K. Schmidt, Edvin Klosi, Michael Chorev, Richard E. Lloyd, Philippe Pierre, Gerhard Wagner, Joseph Ledoux, Eric Klann

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3383-3388
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number8
DOIs
StatePublished - Feb 22 2011

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Eukaryotic Initiation Factor-4G
Eukaryotic Initiation Factor-4E
Long-Term Memory
Amygdala
Fear
Learning
Pharmaceutical Preparations
Proteins
Memory Consolidation
In Vitro Techniques
Inhibition (Psychology)

Keywords

  • Fragments of apoptotic cleavage of eIF4G
  • Internal ribosome entry site-dependent translation

ASJC Scopus subject areas

  • General

Cite this

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation. / Hoeffer, Charles A.; Cowansage, Kiriana K.; Arnold, Elizabeth C.; Banko, Jessica L.; Moerke, Nathan J.; Rodriguez, Ricard; Schmidt, Enrico K.; Klosi, Edvin; Chorev, Michael; Lloyd, Richard E.; Pierre, Philippe; Wagner, Gerhard; Ledoux, Joseph; Klann, Eric.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 8, 22.02.2011, p. 3383-3388.

Research output: Contribution to journalArticle

Hoeffer, Charles A. ; Cowansage, Kiriana K. ; Arnold, Elizabeth C. ; Banko, Jessica L. ; Moerke, Nathan J. ; Rodriguez, Ricard ; Schmidt, Enrico K. ; Klosi, Edvin ; Chorev, Michael ; Lloyd, Richard E. ; Pierre, Philippe ; Wagner, Gerhard ; Ledoux, Joseph ; Klann, Eric. / Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 8. pp. 3383-3388.
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