title: Altered AMPA receptor expression plays an important role in inducing bidirectional synaptic plasticity during contextual fear memory reconsolidation.
abstract: Retrieval of a memory appears to render it unstable until the memory is once again re-stabilized or reconsolidated. Although the occurrence and consequences of reconsolidation have received much attention in recent years, the specific mechanisms that underlie the process of reconsolidation have not been fully described. Here, we present the first electrophysiological model of the synaptic plasticity changes underlying the different stages of reconsolidation of a conditioned fear memory. In this model, retrieval of a fear memory results in immediate but transient alterations in synaptic plasticity, mediated by modified expression of the glutamate receptor subunits GluA1 and GluA2 in the hippocampus of rodents. Retrieval of a memory results in an immediate impairment in LTP, which is enhanced 6h following memory retrieval. Conversely, memory retrieval results in an immediate enhancement of LTD, which decreases with time. These changes in plasticity are accompanied by decreased expression of GluA2 receptor subunits. Recovery of LTP and LTD correlates with progressive overexpression of GluA2 receptor subunits. The contribution of the GluA2 receptor was confirmed by interfering with receptor expression at the postsynaptic sites. Blocking GluA2 endocytosis restored LTP and attenuated LTD during the initial portion of the reconsolidation period. These findings suggest that altered GluA2 receptor expression is one of the mechanisms that controls different forms of synaptic plasticity during reconsolidation.
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Subhrajit
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Department of Psychology, Thach Hall, Auburn University, AL 36849, United States.
authors.forename: Whitney
authors.initials: W
authors.lastname: Kimble
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States; Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
authors.forename: Manal
authors.initials: M
authors.lastname: Buabeid
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Dwipayan
authors.initials: D
authors.lastname: Bhattacharya
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Jenna
authors.initials: J
authors.lastname: Bloemer
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alhowail
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Miranda
authors.initials: M
authors.lastname: Reed
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Muralikrishnan
authors.initials: M
authors.lastname: Dhanasekaran
authors.affiliation: Department of Psychology, Pryale House, Oakland University, Rochester, MI 48309, United States. Electronic address: marthaescobar@oakland.edu.
authors.forename: Martha
authors.initials: M
authors.lastname: Escobar
authors.affiliation: Department of Drug Discovery and Development, 4306 Walker Building, Auburn University, AL 36849, United States.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004705:Endocytosis / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D057846:Cell-Penetrating Peptides; D018091:Receptors, AMPA; C000595429:Tat-GluA2(3Y) peptide
keywords: Depression; Glutamate; Learning; Memory; Plasticity; Potentiation; Reconsolidation