Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence (Nat Neurosci, 2008, 11:1074-1082)

報告日期: 2008/12/05
報告時間: 17:10/18:00
報告學生: 張智華
講評老師: 黃阿敏

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


Eckel-Mahan KL, Phan T, Han S, Wang H, Chan GC, Scheiner ZS, and Storm DR.

Nat Neurosci 11, 1074 - 1082 (2008).


Speaker: Chang, Chih-Hua (張智華)

Commentator: Huang, A-Min, Ph.D.(黃阿敏 老師)

Time: 2008.12.05. 17:10 – 18:00

Place: Room 602



        Circadian oscillations control the behavioral and metabolic processes of most light-sensitive organisms. Circadian phase-shifting interferes with the retention of the hippocampus-dependent memory, which indicates circadian rhythm affects memory consolidation. The cAMP and mitogen-activated protein kinase (MAPK) signal transduction pathways have critical roles in the consolidation of hippocampus-depedent memory. The authors found hippocampal oscillations in MAPK activity were coincident with oscillations in cAMP and Ras activity in the hippocampus. The MAPK activity peaked during the day, which was usually the inactive period for mice. The nadir in MAPK phosphorylation during the circadian cycle coincided with severe deficits in contextual fear memory processing, suggesting that the consolidation process is deficient in mice trained during the night. Furthermore, circadian oscillations in cAMP and MAPK activity were absent in memory-deficient transgenic mice lacking Ca2+-stimulated adenylyl cyclases (AC). Blocking diurnal phosphorylation of MAPK in vivo by U0126, MEK inhibitor, demonstrated that a reduction in the peak of MAPK activity impairs memory persistence. Conversely, the activation of the MAPK pathway during the endogenous nadir by injecting forskolin to stimulate AC activity impaired memory persistence, whereas U0126 had no effect on memory when administered at night. The results suggested that cAMP/MAPK signaling pathway undergoes circadian oscillations in the hippocampus, not merely the presence of phosphorylated MAPK, are required for consolidation and maintenance of contextual memory.


References 1, 2

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2.   Wang, H. & Storm, D.R. Calmodulin-regulated adenylyl cyclases: cross-talk and plasticity in the central nervous system. Mol Pharmacol 63, 463-468 (2003).