Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
J Neurosci. 2013 Apr 10;33(15):6460-8. doi: 10.1523/JNEUROSCI.5018-12.2013.
The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this pathway undergoes a circadian oscillation required for memory persistence that reaches a peak during the daytime. Because mice exhibit polyphasic sleep patterns during the day, this suggested the interesting possibility that cAMP, MAPK activity, and CREB phosphorylation may be elevated during sleep. Here, we report that cAMP, phospho-p44/42 MAPK, and phospho-CREB are higher in rapid eye movement (REM) sleep compared with awake mice but are not elevated in non-REM sleep. This peak of activity during REM sleep does not occur in mice lacking calmodulin-stimulated adenylyl cyclases, a mouse strain that learns but cannot consolidate hippocampus-dependent memory. We conclude that a preferential increase in cAMP, MAPK activity, and CREB phosphorylation during REM sleep may contribute to hippocampus-dependent memory consolidation.
环磷酸腺苷 (cAMP)、丝裂原活化蛋白激酶 (MAPK) 和 cAMP 反应元件结合蛋白 (CREB) 的转录途径是海马依赖性记忆巩固所必需的。在小鼠中，该途径存在昼夜节律性振荡，以维持记忆的持久性，其峰值出现在白天。由于小鼠在白天表现出多相睡眠模式，这表明一个有趣的可能性，即 cAMP、MAPK 活性和 CREB 磷酸化可能在睡眠期间升高。在这里，我们报告在快速眼动 (REM) 睡眠期间 cAMP、磷酸化 p44/42 MAPK 和磷酸化 CREB 高于清醒小鼠，但在非快速眼动睡眠期间没有升高。在缺乏钙调蛋白刺激的腺苷酸环化酶的小鼠中，这种 REM 睡眠期间的活性峰值不会出现，而这种小鼠能够学习但不能巩固海马依赖性记忆。我们得出结论，在 REM 睡眠期间 cAMP、MAPK 活性和 CREB 磷酸化的优先增加可能有助于海马依赖性记忆巩固。
