Episodic-Like Memory for What-Where-Which Occasion is Selectively Impaired in the 3xTgAD Mouse Model of Alzheimer's Disease
Episodic-Like Memory for What-Where-Which Occasion is Selectively Impaired in the 3xTgAD Mouse Model of Alzheimer's Disease
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DOI：
10.3233/jad-2012-121543
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Gigg, John
中科院分区：
文献类型：
--
作者：
Davis, Katherine E.;Easton, Alexander;Gigg, John
情节记忆丧失是早期阿尔茨海默病(AD)的一个重要特征。对老鼠进行的一项类似情节的记忆测试，即What-Where-Which时机任务(WWWhich)，需要将物体、位置和上下文信息联系起来，以形成对事件的综合记忆。WWWhich任务不能通过使用非情景信息来解决，例如对象熟悉度，并且依赖于海马体的完整性。因此，它提供了一个理想的工具，用来测试3xTg小鼠AD模型的情景样记忆能力。由于这个模型捕捉到了人类AD的大部分表型，我们假设这些小鼠在WWWhich情节式记忆任务中会出现缺陷。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WWWhich任务中不需要情节样记忆的部分。这些任务包括物体(新物体识别)、位置(物体位置任务、什么-哪里任务)和语境(什么-什么)记忆，以及另一个可以在不依赖情景回忆(什么-在哪里-什么时候；什么时候)的情况下解决的三组分任务。结果表明，对照组129sv/C57BL6小鼠在6月龄时可形成类似发作的记忆，而3xTgAD小鼠则表现出一定程度的记忆障碍。重要的是，虽然3xTgAD小鼠在空间成分任务上表现出一些缺陷，但它们在更复杂的WwWhen组合任务(包括空间成分，并对非间歇性解决方案开放)中没有受到损害。这些结果有力地表明，以海马结构为中心的AD病理介导了3xTgAD模型中WWWhich事件样记忆的特异性缺陷。
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.