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Nat Neurosci. 2008 Sep;11(9):1074-82.

Circadian oscillation of hippocampal MAPK activity and cAmp: implications for memory persistence.

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  • 1Department of Pharmacology, University of Washington, 1959 NE Pacific St., Seattle, Washington 98195, USA.

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.

Comment in

  • Rhythms of memory. [Nat Neurosci. 2008]
PMID:
19160506
[PubMed - indexed for MEDLINE]
PMCID:
PMC2772165
Free PMC Article

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