INVESTIGADORES
FEDERMAN Maria Noel
artículos
Título:
CALCINEURIN PHOSPHATASE AS A NEGATIVE REGULATOR OF FEAR MEMORY IN HIPPOCAMPUS: CONTROL ON NUCLEAR FACTOR-ΚB SIGNALING IN CONSOLIDATION AND RECONSOLIDATION
Autor/es:
VERÓNICA DE LA FUENTE; NOEL FEDERMAN; MARIA SOL FUSTIÑANA; GISELA ZALCMAN; ARTURO ROMANO
Revista:
Hippocampus
Editorial:
Wiley Online Library
Referencias:
Año: 2014 p. 1549 - 1561
ISSN:
1098-1063
Resumen:
Protein
phosphatases are important regulators of neural plasticity and memory. Some
studies support that the Ca(2+) /calmodulin-dependent phosphatase calcineurin
(CaN) is, on the one hand, a negative regulator of memory formation and, on the
other hand, a positive regulator of memory extinction and reversal learning.
However, the signaling mechanisms by which CaN exerts its action in such
processes are not well understood. Previous findings support that CaN
negatively regulate the nuclear factor kappaB (NF-kB) signaling pathway during
extinction. Here, we have studied the role of CaN in contextual fear memory
consolidation and reconsolidation in the hippocampus. We investigated the CaN
control on the NF-kB signaling pathway, a key mechanism that regulates gene
expression in memory processes. We found that post-training intrahippocampal
administration of the CaN inhibitor FK506 enhanced memory retention one day but
not two weeks after training. Accordingly, the inhibition of CaN by FK506
increased NF-kB activity in dorsal hippocampus. The administration of the NF-kB
signaling pathway inhibitor sulfasalazine (SSZ) 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. Strikingly, memory was also enhanced two
weeks after training, suggesting that reinforcement during reconsolidation is
more persistent than during consolidation. The coadministration of SSZ and
FK506 blocked the enhancement effect in reconsolidation, suggesting that this facilitation
is also dependent on the NF-κB signaling pathway. In summary, our results
support a novel mechanism by which memory formation and reprocessing can be
controlled by CaN regulation on NF-κB activity.