NEGATIVE REGULATORS FOR MEMORY FORMATION AND REPROCESSING AFTER RETRIEVAL

DE LA FUENTE V; FEDERMAN N; FUSTIÑANA MS; ZALCMAN G; ROMANO A

Valdivia, Chile

Congreso; X Annual Meeting Sociedad Chilena de Neurociencias; 2014

Sociedad Xhilena de Neurociencias

Animals are surrounded by a large number of diverse and changing stimuli. However, animals do not remember every perceived stimulus, nor make associations between all the stimuli around them. In that sense, there must be cellular and molecular mechanisms that constrain memory formation. Protein phosphatases are important regulators of neural plasticity and memory. Some studies support that the Ca2+/calmodulin-dependent phosphatase calcineurin (CaN) is a negative regulator of memory formation, although the signaling mechanisms by which CaN exerts its action in such processes are not well understood. The aim of this work was to study the role of CaN in contextual fear memory consolidation and reconsolidation in the hippocampus. We investigated the CaN control on the NF-κB signaling pathway, a key mechanism that regulates gene expression in memory Processes. Post-training intra-hippocampal administration of the CaN inhibitor FK506 enhanced memory retention one day but not two weeks after training. Moreover, the inhibition of CaN by FK506 increased NF-κB activity in dorsal hippocampus. The administration of the NF-κB signaling pathway inhibitor sulfasalazine impeded the enhancing effect of FK506. In line with our findings in consolidation, FK506 administration before memory reactivation enhanced memory reconsolidation when tested one day after re-exposure to the training context and also two weeks after training. The co-administration of and FK506 blocked the enhancement effect in reconsolidation, suggesting that this facilitation is also dependent on the NF-κB pathway. Our results support a novel mechanism by which memory formation and reprocessing can be controlled by CaN. regulation on NF-κB activity.