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Mol Brain ; 4: 9, 2011 Feb 11.
Article in English | MEDLINE | ID: mdl-21314917

ABSTRACT

BACKGROUND: Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. RESULTS: We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1) and L-type voltage gated calcium channels (LVGCCs) in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. CONCLUSIONS: Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.


Subject(s)
Gene Expression , Maze Learning/physiology , Memory/physiology , Space Perception/physiology , Animals , Anisomycin/pharmacology , Calcium Channel Blockers/pharmacology , Cannabinoid Receptor Antagonists , Conditioning, Classical , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Fear/physiology , Hippocampus/physiology , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Piperidines/pharmacology , Protein Biosynthesis , Protein Synthesis Inhibitors/pharmacology , Pyrazoles/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Rimonabant , Space Perception/drug effects , Verapamil/pharmacology
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