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Abstract:

Protein phosphatases are important regulators of neural plasticity and memory. Some studies support that the Ca2+/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-κB) 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-κB 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-κB activity in dorsal hippocampus. The administration of the NF-κB 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. © 2014 Wiley Periodicals, Inc.

Registro:

Documento: Artículo
Título:Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation
Autor:de la Fuente, V.; Federman, N.; Fustiñana, M.S.; Zalcman, G.; Romano, A.
Filiación:Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 664058, Switzerland
Palabras clave:Calcineurin; Consolidation; Fear conditioning; Hippocampus; NF-κB; Reconsolidation; calcineurin; immunoglobulin enhancer binding protein; salazosulfapyridine; tacrolimus; calcineurin inhibitor; calcineurin phosphatase; central nervous system agents; immunoglobulin enhancer binding protein; phosphatase; salazosulfapyridine; tacrolimus; animal experiment; animal tissue; Article; controlled study; dorsal hippocampus; facilitation; fear conditioning test; hippocampus; male; memory consolidation; mouse; nonhuman; recall; reinforcement; signal transduction; animal; antagonists and inhibitors; C57BL mouse; conditioned reflex; drug effects; electric shock; fear; hippocampus; memory; metabolism; neuropsychological test; physiology; Animals; Calcineurin Inhibitors; Central Nervous System Agents; Conditioning, Classical; Electroshock; Fear; Hippocampus; Male; Memory; Mice, Inbred C57BL; Neuropsychological Tests; NF-kappa B; Phosphoric Monoester Hydrolases; Signal Transduction; Sulfasalazine; Tacrolimus
Año:2014
Volumen:24
Número:12
Página de inicio:1549
Página de fin:1561
DOI: http://dx.doi.org/10.1002/hipo.22334
Título revista:Hippocampus
Título revista abreviado:Hippocampus
ISSN:10509631
CODEN:HIPPE
CAS:calcineurin, 137951-12-3; salazosulfapyridine, 599-79-1; tacrolimus, 104987-11-3; phosphatase, 9013-05-2; Calcineurin Inhibitors; calcineurin phosphatase; Central Nervous System Agents; NF-kappa B; Phosphoric Monoester Hydrolases; Sulfasalazine; Tacrolimus
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10509631_v24_n12_p1549_delaFuente

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Citas:

---------- APA ----------
de la Fuente, V., Federman, N., Fustiñana, M.S., Zalcman, G. & Romano, A. (2014) . Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation. Hippocampus, 24(12), 1549-1561.
http://dx.doi.org/10.1002/hipo.22334
---------- CHICAGO ----------
de la Fuente, V., Federman, N., Fustiñana, M.S., Zalcman, G., Romano, A. "Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation" . Hippocampus 24, no. 12 (2014) : 1549-1561.
http://dx.doi.org/10.1002/hipo.22334
---------- MLA ----------
de la Fuente, V., Federman, N., Fustiñana, M.S., Zalcman, G., Romano, A. "Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation" . Hippocampus, vol. 24, no. 12, 2014, pp. 1549-1561.
http://dx.doi.org/10.1002/hipo.22334
---------- VANCOUVER ----------
de la Fuente, V., Federman, N., Fustiñana, M.S., Zalcman, G., Romano, A. Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation. Hippocampus. 2014;24(12):1549-1561.
http://dx.doi.org/10.1002/hipo.22334