Article abstract
Nature Neuroscience 11, 1074 - 1082 (2008)
Published online: 10 August 2008 | doi:10.1038/nn.2174
Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence
Kristin L Eckel-Mahan1, Trongha Phan1, Sung Han1, Hongbing Wang2, Guy C-K Chan1, Zachary S Scheiner1 & Daniel R Storm1
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.
- Department of Pharmacology, University of Washington, 1959 NE Pacific St., Seattle, Washington 98195, USA.
- Department of Physiology, Michigan State University, 1200 E. Michigan Avenue, East Lansing, Michigan 48824, USA.
Correspondence to: Daniel R Storm1 e-mail: dstorm@u.washington.edu
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