Reiserer R S, Harrison F E, Syverud D C, McDonald M P
Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-0325, USA.
Genes Brain Behav. 2007 Feb;6(1):54-65. doi: 10.1111/j.1601-183X.2006.00221.x.
Mice co-expressing the Swedish amyloid precursor protein mutation (APP(Swe)) and exon 9 deletion (DeltaE9) of the PSEN1 gene begin to develop amyloid plaques at 6-7 months of age. We demonstrate here a spatial learning deficit in 7-month-old APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze. Mice were first trained on a cued target followed by a hidden-target condition. Although bigenic mice quickly learned the cued-target version of the task, they were significantly impaired when switched to the hidden-target version. In contrast, a separate group of double-transgenic mice trained first on the spatial hidden-target version of the task were unimpaired relative to wild-type controls. We propose that processes such as general rule learning, context learning and exploratory habituation exert a greater influence when the testing environment is novel and overshadow the spatial memory deficit in naive bigenic mice. However, when cued-target training is conducted first, these processes habituate and the spatial learning deficit is unmasked. Seven-month-old APP(Swe) + PSEN1DeltaE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.
共表达瑞典淀粉样前体蛋白突变（APP(Swe)）和早老素1基因第9外显子缺失（DeltaE9）的小鼠在6 - 7月龄时开始出现淀粉样斑块。我们在此使用改良的巴恩斯迷宫证明了7月龄的APP(Swe) + PSEN1DeltaE9双转基因小鼠存在空间学习缺陷。小鼠首先在有线索提示的目标任务上接受训练，随后进行隐藏目标任务。虽然双转基因小鼠很快学会了有线索提示的目标任务版本，但当切换到隐藏目标版本时，它们明显受损。相比之下，另一组首先在空间隐藏目标任务版本上接受训练的双转基因小鼠相对于野生型对照未受损害。我们提出，当测试环境新颖时，诸如一般规则学习、情境学习和探索性习惯化等过程会产生更大影响，并掩盖了未接触过实验的双转基因小鼠的空间记忆缺陷。然而，当先进行有线索提示的目标训练时，这些过程会习惯化，空间学习缺陷就会显现出来。7月龄的APP(Swe) + PSEN1DeltaE9小鼠在不涉及学习空间关联规则的记忆测试中未受损害。
