期刊
NATURE NEUROSCIENCE
卷 11, 期 9, 页码 1074-1082出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2174
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资金
- US National Institutes of Health [NS 20498]
- Ruth L. Kirschstein US National Institutes of Health Research [1 F31 MH075489-01A1]
- Korea Research Foundation Grant for Young Scientists [KRF-2005-213-C00036]
- National Research Foundation of Korea [2005-213-C00036] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) signal transduction pathways have critical roles in the consolidation of hippocampus-dependent memory. We found that extracellular regulated kinase 1/2 MAPK phosphorylation and cAMP underwent a circadian oscillation in the hippocampus that was paralleled by changes in Ras activity and the phosphorylation of MAPK kinase and cAMP response element-binding protein (CREB). The nadir of this activation cycle corresponded with severe deficits in hippocampus-dependent fear conditioning under both light-dark and free-running conditions. Circadian oscillations in cAMP and MAPK activity were absent in memory-deficient transgenic mice that lacked Ca(2+)-stimulated adenylyl cyclases. Furthermore, physiological and pharmacological interference with oscillations in MAPK phosphorylation after the cellular memory consolidation period impaired the persistence of hippocampus-dependent memory. These data suggest that the persistence of long-term memories may depend on reactivation of the cAMP/MAPK/CREB transcriptional pathway in the hippocampus during the circadian cycle.
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