Characteristics of the Reminder that Triggers Object Recognition Memory Reconsolidation in Mice

Abstract

Memories are initially labile and become stable through consolidation. Once consolidated, a memory can be destabilized by a reminder, requiring reconsolidation to become stable again. Memory reconsolidation has been evidenced in several learning tasks, including novel object recognition (NOR). But the features of the reminder that trigger memory destabilization and reconsolidation in this task are poorly characterized. Memory reconsolidation can be evidenced by delivering either an amnesic agent or a memory enhancer after reactivation and testing the resulting long-term memory alteration. Here we trained male mice for 15 min to induce a strong memory formation. Sulfasalazine, a specific inhibitor of the NF-κB pathway, was administered as an amnesic agent in the dorsal hippocampus. NF-κB is a key transcription factor required for consolidation and reconsolidation. We found that reconsolidation was induced when animals were re-exposed for 5 min to a combination of novel and familiar objects, but not to either two familiar or two novel objects. No destabilization was induced by re-exposure to the context without objects. Re-exposure to a combination of novel and familiar objects induced destabilization with a reactivation session as brief as 1 min. One minute of training induced a weak memory that could be enhanced by sodium butyrate, an inhibitor of histone deacetylases (HDACs), after 1 min of re-exposure. Histone acetylation is an epigenetic mechanism involved in gene expression regulation which positively correlates with memory. Thus, in this study we have performed an accurate characterization of the features of the reminder effective in triggering hippocampal NF-κB-dependent reconsolidation.