title: Memory retrieval requires ongoing protein synthesis and NMDA receptor activity-mediated AMPA receptor trafficking.
abstract: Whereas consolidation and reconsolidation are considered dynamic processes requiring protein synthesis, memory retrieval has long been considered a passive readout of previously established plasticity. However, previous findings suggest that memory retrieval may be more dynamic than previously thought. This study therefore aimed at investigating the molecular mechanisms underlying memory retrieval in the rat. Infusion of protein synthesis inhibitors (rapamycin or anisomycin) in the amygdala 10 min before memory retrieval transiently impaired auditory fear memory expression, suggesting ongoing protein synthesis is required to enable memory retrieval. We then investigated the role of protein synthesis in NMDA receptor activity-mediated AMPA receptor trafficking. Coinfusion of an NMDA receptor antagonist (ifenprodil) or infusion of an AMPA receptor endocytosis inhibitor (GluA23Y) before rapamycin prevented this memory impairment. Furthermore, rapamycin transiently decreased GluA1 levels at the postsynaptic density (PSD), but did not affect extrasynaptic sites. This effect at the PSD was prevented by an infusion of GluA23Y before rapamycin. Together, these data show that ongoing protein synthesis is required before memory retrieval is engaged, and suggest that this protein synthesis may be involved in the NMDAR activity-mediated trafficking of AMPA receptors that takes place during memory retrieval.
authors: Department of Psychology, McGill University, Montreal, Quebec H3A 1B1, Canada joelle.lopez@douglas.mcgill.ca.
authors: Joëlle
authors: J
authors: Lopez
authors: Department of Psychology, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors: Karine
authors: K
authors: Gamache
authors: Department of Psychology, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors: Rilla
authors: http://orcid.org/0000-0002-0521-5129
authors: R
authors: Schneider
authors: Department of Psychology, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors: Karim
authors: K
authors: Nader
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D020123:Sirolimus
keywords: AMPAR trafficking; fear conditioning; memory; protein synthesis; rat; retrieval