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

被引：270

作者：

Eckel-Mahan, Kristin L. ^{[1
]}

Phan, Trongha ^{[1
]}

Han, Sung ^{[1
]}

Wang, Hongbing ^{[2
]}

Chan, Guy C-K ^{[1
]}

Scheiner, Zachary S. ^{[1
]}

Storm, Daniel R. ^{[1
]}

机构：

[1] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

[2] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA

来源：

NATURE NEUROSCIENCE | 2008年 / 11卷 / 09期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nn.2174

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1074 / 1082

页数：9

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