Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation
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 rev...
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| Formato: | JOUR |
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_10509631_v24_n12_p1549_delaFuente |
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todo:paper_10509631_v24_n12_p1549_delaFuente2023-10-03T16:00:29Z Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation de la Fuente, V. Federman, N. Fustiñana, M.S. Zalcman, G. Romano, A. 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 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. Fil:de la Fuente, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Federman, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fustiñana, M.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Zalcman, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Romano, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10509631_v24_n12_p1549_delaFuente |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
de la Fuente, V. Federman, N. Fustiñana, M.S. Zalcman, G. Romano, A. |
| author_facet |
de la Fuente, V. Federman, N. Fustiñana, M.S. Zalcman, G. Romano, A. |
| author_sort |
de la Fuente, V. |
| title |
Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation |
| title_short |
Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation |
| title_full |
Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation |
| title_fullStr |
Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation |
| title_full_unstemmed |
Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: Control on nuclear factor-κB signaling in consolidation and reconsolidation |
| title_sort |
calcineurin phosphatase as a negative regulator of fear memory in hippocampus: control on nuclear factor-κb signaling in consolidation and reconsolidation |
| url |
http://hdl.handle.net/20.500.12110/paper_10509631_v24_n12_p1549_delaFuente |
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