Comparative dynamics of MAPK/ERK signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval
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Over the past few years multiple studies have attempted to uncover molecular signatures of memory reconsolidation when compared to consolidation. In the present study we used immunocytochemical detection of the MAPK/ERK1/2 pathway, to track activated neuronal circuits in the hippocampus and amygdala recruited during the consolidation and reconsolidation of a contextual fear conditioning (CFC) memory. We report selective differences in magnitude and temporal dynamics of activated ERK1/2 signalling in different subregions of these two structures between the post-training and post-retrieval periods, except in the dentate gyrus, where the patterns of activation were similar. We then focused on this brain area to dissect out the patterns of downstream ERK1/2 signalling components, including the phosphorylation of MSK-1 and histone H3 on ser10, along with the induction of the Immediate Early Genes (IEGs) Arc/Arg3.1, c-Fos and Zif268/Egr1 following CFC training and retrieval. We found that the completion of the nucleosomal response as well as the induction of IEGs shorter during the reconsolidation period as compared to consolidation. Our results shed new light on the cellular mechanisms underlying the consolidation and reconsolidation processes engaged following CFC training and retrieval and further extend the notion that memory reconsolidation is not mechanistically a repetition of consolidation. In addition, we provide evidence that the strength of a previously established CFC memory is characterized by distinct patterns of ERK1/2 activation in different hippocampal and amygdalar subfields upon CFC memory recall. Our results emphasize the differences between consolidation and reconsolidation processes in relation to contextual fear memories.
KeywordsComparative distribution Memory consolidation and reconsolidation Phospho-ERK Phospho-H3 c-Fos Zif268 Arc/Arg3.1 Kinetics
Contextual fear conditioning
cAMP response element
Extracellular-signal Regulated Kinase
Immediate early gene
Mitogen-activated protein Kinase
MAPK ERK kinase
Mitogen and Stressed-activated protein Kinase
This work has been supported by the “Centre National de la Recherche Scientifique” (CNRS), l’ “Agence Nationale pour la Recherche” (ANR-08-BLAN) and the “Fondation Jerôme Lejeune”. A.B. has been supported by the Edmond Rothschild Chemical Dependency Institute Beth Israël Medical center and Fondation pour la Recherche Médicale.
Conflict of interest
All authors report no conflict of interest.
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