title: Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory.
abstract: Signaling at NMDA receptors (NMDARs) is known to be important for memory reconsolidation, but while most studies show that NMDAR antagonists prevent memory restabilization and produce amnesia, others have shown that GluN2B-selective NMDAR antagonists prevent memory destabilization, protecting the memory. These apparently paradoxical, conflicting data provide an opportunity to define more precisely the requirement for different NMDAR subtypes in the mechanisms underlying memory reconsolidation and to further understand the contribution of glutamatergic signaling to this process. Here, using rats with fully consolidated pavlovian auditory fear memories, we demonstrate a double dissociation in the requirement for GluN2B-containing and GluN2A-containing NMDARs within the basolateral amygdala in the memory destabilization and restabilization processes, respectively. We further show a double dissociation in the mechanisms underlying memory retrieval and memory destabilization, since AMPAR antagonism prevented memory retrieval while still allowing the destabilization process to occur. These data demonstrate that glutamatergic signaling mechanisms within the basolateral amygdala differentially and dissociably mediate the retrieval, destabilization, and restabilization of previously consolidated fear memories.
authors: Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom. alm46@cam.ac.uk
authors: Amy L
authors: AL
authors: Milton
authors: Emiliano
authors: E
authors: Merlo
authors: Patrizia
authors: P
authors: Ratano
authors: Ben L
authors: BL
authors: Gregory
authors: Jessica K
authors: JK
authors: Dumbreck
authors: Barry J
authors: BJ
authors: Everitt
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001245:Association Learning / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000841:Anisomycin; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; C121001:NR2B NMDA receptor; C010739:ifenprodil