Long-term memory for place learning is facilitated by expression of cAMP response element-binding protein in the dorsal hippocampus
Long-term memory for place learning is facilitated by expression of cAMP response element-binding protein in the dorsal hippocampus
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DOI：
10.1101/lm.395407
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发表时间：
2007-03-01
影响因子：
2
通讯作者：
Colombo, Paul J.
中科院分区：
文献类型：
--
作者：
Brightwell, Jennifer J.;Smith, Clayton A.;Colombo, Paul J.
大量研究表明，海马体对于巩固啮齿动物的长期空间记忆是必要的。我们之前报道过，使用位置策略解决交叉迷宫任务的大鼠显示海马环AMP反应元件结合蛋白（CREB）持续磷酸化，CREB是一种与长期记忆形成有关的转录因子。在当前的研究中，我们使用病毒载体介导的基因转移来验证一个假设，即地点学习长期记忆的形成可以通过增加海马背侧CREB的水平来促进。海马内灌注3天后，实验大鼠（HSV-CREB）和对照大鼠（HSV-LacZ；生理盐水）在水交叉迷宫中进行单次地点任务训练。5 d后对大鼠进行记忆测试。各组大鼠均表现出短时记忆，各处理组在习得过程中无显著差异。然而，只有注射hsv - creb的大鼠在训练和测试之间表现出显著的储蓄，而注射HSV-LacZ和盐水的大鼠则没有。定量Western blotting证实，与对照组相比，注射HSV-CREB的大鼠在训练期间海马背侧CREB水平升高。目前的研究结果表明，长期记忆的形成可以通过增加海马CREB蛋白的水平来促进。
Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein ( CREB), a transcription factor implicated in long-term memory formation. In the current study, we used viral vector-mediated gene transfer to test the hypothesis that formation of long-term memory for place learning can be facilitated by increasing levels of CREB in the dorsal hippocampus. Three days after intrahippocampus infusion, experimental (HSV-CREB) and control (HSV-LacZ; saline) rats were trained during a single session on a place task in a water cross maze. Rats were tested for memory 5 d later. Rats in all groups showed short-term memory, and there were no significant differences among treatment groups during acquisition. However, only HSV-CREB-infused rats showed significant savings between training and test, while HSV-LacZ- and saline-treated rats did not. Quantitative Western blotting confirmed that levels of dorsal hippocampus CREB were increased during training in rats infused with HSV-CREB in comparisons with controls. The present results show that formation of long-term memory can be facilitated by increasing levels of hippocampus CREB protein.