Centre de Neurosciences Intégratives et Cognitives, Talence, France.
Hippocampus. 2011 Nov;21(11):1169-79. doi: 10.1002/hipo.20844. Epub 2010 Sep 16.
Although the importance of cAMP-response element binding protein (CREB) phosphorylation in long-term memory formation is well documented for hippocampus-dependent tasks, little is known about the changes in phosphorylated CREB (pCREB) that occur during the process of extinction. The purpose of this study was to characterize the temporal patterns of pCREB in the CA1 and the amygdala after the extinction of previously acquired spatial information in the water maze. Mice were trained to find a hidden platform located at a fixed position and then were given extinction sessions in which the platform was either absent (NoPF) or relocated every day (RandomPF). We show that water maze spatial training evoked a biphasic response of pCREB in the CA1, with two different peaks occurring 15 min and 8 h postacquisition. The extinction of the original spatial preference significantly reduced the two peaks of CA1 pCREB in both RandomPF and NoPF groups whereas CA1 pCREB at 60 min post-training remained unaffected. Moreover, the early and late phases of extinction training produced regionally dissociable effects on pCREB in the CA1 and the lateral nucleus of the amygdala. These findings provide new insights on the molecular dynamics and anatomical dissociations underlying spatial memory and extinction learning.
尽管环磷腺苷反应元件结合蛋白（CREB）磷酸化在海马依赖性任务的长期记忆形成中的重要性已得到充分证明，但对于在消退过程中发生的磷酸化 CREB（pCREB）的变化知之甚少。本研究的目的是描述在水迷宫中先前获得的空间信息的消退过程中 CA1 和杏仁核中 pCREB 的时间模式。将小鼠训练为在固定位置找到隐藏平台，然后进行消退训练，其中平台要么不存在（NoPF），要么每天重新定位（RandomPF）。我们发现，水迷宫空间训练在 CA1 中引发了 pCREB 的双相反应，在获得后 15 分钟和 8 小时出现两个不同的峰值。原始空间偏好的消退显著降低了 RandomPF 和 NoPF 组中 CA1 pCREB 的两个峰值，而训练后 60 分钟的 CA1 pCREB 则不受影响。此外，消退训练的早期和晚期阶段在 CA1 和杏仁核外侧核中对 pCREB 产生了区域分离的影响。这些发现为空间记忆和消退学习的分子动力学和解剖分离提供了新的见解。
