Episodic memory loss is a defining feature of early-stage Alzheimer's disease (AD). A test of episodic-like memory for the rat, the What-Where-Which occasion task (WWWhich), requires the association of object, location, and contextual information to form an integrated memory for an event. The WWWhich task cannot be solved by use of non-episodic information such as object familiarity and is dependent on hippocampal integrity. Thus, it provides an ideal tool with which to test capacity for episodic-like memory in the 3xTg murine model for AD. As this model captures much of the human AD phenotype, we hypothesized that these mice would show a deficit in the WWWhich episodic-like memory task. To test the specificity of any episodic-like deficit, we also examined whether mice could perform components of the WWWhich task that do not require episodic-like memory. These included object (Novel Object Recognition), location (Object Location Task, What-Where task), and contextual (What-Which) memory, as well as another three-component task that can be solved without reliance on episodic recall (What-Where-When; WWWhen). The results demonstrate for the first time that control 129sv/c57bl6 mice could form WWWhich episodic-like memories, whereas, 3xTgAD mice at 6 months of age were impaired. Importantly, while 3xTgAD mice showed some deficit on spatial component tasks, they were unimpaired in the more complex WWWhen combination task (which includes a spatial component and is open to non-episodic solutions). These results strongly suggest that AD pathology centered on the hippocampal formation mediates a specific deficit for WWWhich episodic-like memory in the 3xTgAD model.

译文

偶发性记忆丧失是早期阿尔茨海默氏病 (AD) 的一个决定性特征。对rat的类似情景记忆的测试,即What-Where-whit场合任务 (wwwhit),需要将对象,位置和上下文信息关联起来,以形成事件的集成记忆。Wwwhit任务无法通过使用非情节信息 (例如对象熟悉度) 来解决,并且取决于海马的完整性。因此,它提供了一种理想的工具,可以用来测试AD的3xTg鼠模型中类似情节的记忆能力。由于该模型捕获了许多人类AD表型,因此我们假设这些小鼠在www中会显示出类似情节的记忆任务的缺陷。为了测试任何情节样缺陷的特异性,我们还检查了小鼠是否可以执行不需要情节样记忆的wwwhat任务的组成部分。其中包括对象 (新颖的对象识别),位置 (对象位置任务,What-Where任务) 和上下文 (What-Where) 记忆,以及另一个无需依赖情节回忆即可解决的三部分任务 (What-Where; Wwwhy)。结果首次表明,对照129sv/c57bl6小鼠可以形成情节样记忆,而6个月大的3xTgAD小鼠则受到损害。重要的是,虽然3xTgAD小鼠在空间组件任务上显示出一些缺陷,但它们在更复杂的wwiw组合任务 (包括空间组件,并且对非偶发解决方案开放) 中并未受到损害。这些结果强烈表明,以海马结构为中心的AD病理在3xtgad模型中介导了www的特定缺陷,即情景样记忆。

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