Calcineurin phosphatase as a negative regulator of fear memory: control on NF-kB signaling

DE LA FUENTE, VERÓNICA; FEDERMAN, NOEL; FUSTIÑANA, MARIA SOL; ZALCMAN, GISELA; ROMANO, ARTURO

Munich

Congreso; European Brain and Behaviour Society Meeting; 2013

European Brain and Behaviour Society

Protein phosphatases are important regulators of neural plasticity and memory. Several studies supports that the Ca2+/calmoduline-dependent phosphatase calcineurin (CaN) is a negative regulator of memory formation and a positive regulator of memory extinction and reversal learning. However, the signaling mechanisms by which CaN exerts its action in these processes are not well understood. Here we studied the role of CaN in contextual fear memory consolidation in hippocampus and its role in reconsolidation. As well, we studied the CaN control on the nuclear factor kappaB (NF-κB) signaling pathway, a key mechanism of gene expression in memory processes. We found that post-training intrahipocampal administration of the CaN inhibitor FK506 enhanced memory retention 1 day but not 2 weeks after training. Contrarily, the administration of the NF-κB inhibitor sulfasalazine (SSZ) impaired memory retention at both 1 day and 14 days after training. Furthermore, the co-administration of SSZ and FK506 impeded the enhancing effect of CaN inhibition. Accordingly with our findings in consolidation, the administration of FK506 previous to memory reactivation enhanced memory reconsolidation when tested 1 day after reexposure to the training context. However, and strikingly, memory was also enhanced 2 weeks later, suggesting that memory reinforcement during reconsolidation is more persistent than during consolidation. The co-administration of SSZ and FK506 blocked the enhancement effect in reconsolidation, indicating that this facilitation is also dependent on NF-κB signaling pathway. In summary, our results propose a novel mechanism by which memory formation and reprocessing can be controlled by CaN regulation on NF-kB activity.