Circadian oscillation of hippocampal MAPK activity and cAmp: implications for memory persistence.
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.
Eckel-Mahan
Kristin L
KL
Department of Pharmacology, University of Washington, 1959 NE Pacific St., Seattle, Washington 98195, USA.
Phan
Trongha
T
Han
Sung
S
Wang
Hongbing
H
Chan
Guy C K
GC
Scheiner
Zachary S
ZS
Storm
Daniel R
DR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D002070:Butadienes / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000008:administration & dosage; D002940:Circadian Rhythm / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000172:deficiency / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000172:deficiency / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium