Hebda-Bauer Elaine K, Watson Stanley J, Akil Huda
Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Learn Mem. 2005 Sep-Oct;12(5):461-71. doi: 10.1101/lm.94105. Epub 2005 Sep 15.
The impact of a previously successful or unsuccessful experience on the subsequent acquisition of a related task is not well understood. The nature of past experience may have even greater impact in individuals with learning deficits, as their cognitive processes can be easily disrupted. Mice with a targeted disruption of the alpha and delta isoforms of the cAMP-response element-binding protein (CREB) gene (CREB(alphadelta-)-deficient mice) have a genetic vulnerability to impaired learning and memory that is highly influenced by experimental conditions. Thus, we studied the impact of prior successful and unsuccessful experiences on the degree to which CREB(alphadelta-)-deficient mice exhibit impaired spatial learning and memory in the Morris water maze (MWM). In Experiment 1, we replicated the cognitive deficit of CREB(alphadelta-)-deficient mice when given two trials per day with a 1-min intertrial interval (MWM2), and labeled this experience as a "failure." We rescued the deficit using four trials per day with a 3- to 5-min intertrial interval (MWM4) and labeled this experience a "success." In Experiment 2, a new, naive set of wild-type (WT) and CREB(alphadelta-)-deficient mice were randomly assigned to one of two sequence protocols to assess the influence of a success or a failure on subsequent performance. In Group 1, mice were first exposed to the MWM4 condition, followed by the more difficult MWM2 task. As expected, CREB(alphadelta-)-deficient mice performed well in the MWM4; they also performed well during reversal testing (MWM4R) where the goal location is changed. With this initial successful learning experience, the CREB(alphadelta-)-deficient mice then performed as well as WT mice in the MWM2, the condition in which they are known to be impaired. In contrast, CREB(alphadelta-)-deficient mice in Group 2 had an unsuccessful experience when first exposed to the MWM2 condition, and then also showed impairment in the MWM4, the condition in which they would normally perform well. This deficit was amplified when CREB(alphadelta-)-deficient mice were then tested in the reversal test. Sex differences in learning among CREB(alphadelta-)-deficient mice were amplified upon exposure to an unsuccessful learning experience. These data indicate that, under conditions of cognitive impairment, past experience can-depending on its nature-significantly facilitate or hinder future performance.
先前成功或失败的经历对后续相关任务习得的影响尚未得到充分理解。过去经历的性质可能对有学习缺陷的个体产生更大影响，因为他们的认知过程很容易受到干扰。靶向破坏环磷酸腺苷反应元件结合蛋白（CREB）基因的α和δ亚型的小鼠（CREB（αδ-）缺陷小鼠）具有遗传易感性，其学习和记忆受损受到实验条件的高度影响。因此，我们研究了先前成功和失败的经历对CREB（αδ-）缺陷小鼠在莫里斯水迷宫（MWM）中表现出空间学习和记忆受损程度的影响。在实验1中，当每天给予两次试验且试验间隔为1分钟（MWM2）时，我们重现了CREB（αδ-）缺陷小鼠的认知缺陷，并将这种经历标记为“失败”。我们通过每天进行四次试验且试验间隔为3至5分钟（MWM4）来挽救这种缺陷，并将这种经历标记为“成功”。在实验2中，一组新的、未经训练的野生型（WT）和CREB（αδ-）缺陷小鼠被随机分配到两种序列方案之一，以评估成功或失败对后续表现的影响。在第1组中，小鼠首先暴露于MWM4条件，然后是更困难的MWM2任务。正如预期的那样，CREB（αδ-）缺陷小鼠在MWM4中表现良好；在目标位置改变的反转测试（MWM4R）中，它们也表现良好。有了这种最初的成功学习经历后，CREB（αδ-）缺陷小鼠在MWM2中的表现与WT小鼠一样好，而它们在MWM2中通常是受损的。相比之下，第2组中的CREB（αδ-）缺陷小鼠在首次暴露于MWM2条件时经历了失败，然后在MWM4中也表现出受损，而它们在MWM4中通常会表现良好。当CREB（αδ-）缺陷小鼠随后在反转测试中接受测试时，这种缺陷被放大。CREB（αδ-）缺陷小鼠在学习上的性别差异在经历失败的学习经历后被放大。这些数据表明，在认知障碍的情况下，过去的经历根据其性质可以显著促进或阻碍未来的表现。
