| First Author | Eckel-Mahan KL | Year | 2008 |
| Journal | Nat Neurosci | Volume | 11 |
| Issue | 9 | Pages | 1074-82 |
| PubMed ID | 19160506 | Mgi Jnum | J:140861 |
| Mgi Id | MGI:3814756 | Doi | 10.1038/nn.2174 |
| Citation | Eckel-Mahan KL, et al. (2008) Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence. Nat Neurosci |
| abstractText | 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. |
