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.

中文翻译：

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海马 MAPK 活动和 cAmp 的昼夜节律振荡：对记忆持久性的影响。

丝裂原活化蛋白激酶 (MAPK) 和环磷酸腺苷 (cAMP) 信号转导通路在巩固海马依赖性记忆中具有关键作用。我们发现细胞外调节激酶 1/2 MAPK 磷酸化和 cAMP 在海马中经历昼夜节律振荡，与 Ras 活性的变化以及 MAPK 激酶和 cAMP 反应元件结合蛋白 (CREB) 的磷酸化平行。这个激活周期的最低点与在明暗和自由运行条件下海马依赖性恐惧条件反射的严重缺陷相对应。在缺乏 Ca2+ 刺激的腺苷酸环化酶的记忆缺陷转基因小鼠中不存在 cAMP 和 MAPK 活性的昼夜节律振荡。此外，在细胞记忆巩固期后对 MAPK 磷酸化振荡的生理和药理学干扰会损害海马依赖性记忆的持久性。这些数据表明，长期记忆的持久性可能取决于昼夜节律周期中海马中 cAMP/MAPK/CREB ​​转录通路的重新激活。