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Genetic disruption of the core circadian clock impairs hippocampus-dependent memory
Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. B...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105720/ https://www.ncbi.nlm.nih.gov/pubmed/25034823 http://dx.doi.org/10.1101/lm.035451.114 |
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author | Wardlaw, Sarah M. Phan, Trongha X. Saraf, Amit Chen, Xuanmao Storm, Daniel R. |
author_facet | Wardlaw, Sarah M. Phan, Trongha X. Saraf, Amit Chen, Xuanmao Storm, Daniel R. |
author_sort | Wardlaw, Sarah M. |
collection | PubMed |
description | Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1(−/−) mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1(−/−) mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1(−/−) mice is also significantly decreased relative to that from wild-type mice. Activation of Erk(1,2) MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1(−/−) mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1. |
format | Online Article Text |
id | pubmed-4105720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41057202015-08-01 Genetic disruption of the core circadian clock impairs hippocampus-dependent memory Wardlaw, Sarah M. Phan, Trongha X. Saraf, Amit Chen, Xuanmao Storm, Daniel R. Learn Mem Research Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1(−/−) mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1(−/−) mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1(−/−) mice is also significantly decreased relative to that from wild-type mice. Activation of Erk(1,2) MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1(−/−) mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1. Cold Spring Harbor Laboratory Press 2014-08 /pmc/articles/PMC4105720/ /pubmed/25034823 http://dx.doi.org/10.1101/lm.035451.114 Text en © 2014 Wardlaw et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Wardlaw, Sarah M. Phan, Trongha X. Saraf, Amit Chen, Xuanmao Storm, Daniel R. Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title | Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title_full | Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title_fullStr | Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title_full_unstemmed | Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title_short | Genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
title_sort | genetic disruption of the core circadian clock impairs hippocampus-dependent memory |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105720/ https://www.ncbi.nlm.nih.gov/pubmed/25034823 http://dx.doi.org/10.1101/lm.035451.114 |
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