title: 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.
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hoeffer
authors.forename: Kiriana K
authors.initials: KK
authors.lastname: Cowansage
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Arnold
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Banko
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Moerke
authors.forename: Ricard
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Enrico K
authors.initials: EK
authors.lastname: Schmidt
authors.forename: Edvin
authors.initials: E
authors.lastname: Klosi
authors.forename: Michael
authors.initials: M
authors.lastname: Chorev
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lloyd
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Joseph E
authors.initials: JE
authors.lastname: LeDoux
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
mesh_terms: D000679:Amygdala; D000818:Animals; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D057567:Memory, Long-Term; D009473:Neuronal Plasticity; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D011500:Protein Synthesis Inhibitors