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- Title
Circadian oscillation of hippocampal MAPK activity and cAmp: implications for memory persistence.
- Authors
Eckel-Mahan, Kristin L; Phan, Trongha; Han, Sung; Wang, Hongbing; Chan, Guy C K; Scheiner, Zachary S; Storm, Daniel R
- Abstract
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 Ca2+ -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.
- Publication
Nature neuroscience, 2008, Vol 11, Issue 9, p1074
- ISSN
1546-1726
- Publication type
Journal Article
- DOI
10.1038/nn.2174