Episodic-like memory in mice: Simultaneous assessment of object, place and temporal order memory

Ekrem Dere, Joseph P. Huston, Maria A. De Souza Silva
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引用次数: 223

Abstract

Episodic memory refers to the conscious recollection of a unique past experience in terms of “what” happened and “where” and “when” it happened. Since deficits in episodic memory are found in a number of neuropsychiatric diseases, such as Alzheimer's disease, for which several pharmacological, lesion and genetic animal models are available, there is a need for animal models of episodic-like memory, which can be used to devise appropriate treatments. However, even when the problem of conscious recollection in animals is factored out, episodic memory has been difficult to demonstrate in nonhuman mammals because it has not yet been possible to demonstrate an integrated memory for “what”,-“where”-and-“when”.

We designed a three-trial “what”,-“where”-and-“when” object exploration task in which different versions of the novelty preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored and (c) the temporal order memory for objects presented at distinct time points. Our results suggest that mice are able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered and (c) discriminate the relative recency in which different objects were presented. We suggest that our protocol providing the simultaneous assessment of object memory for “what”,-“where”-and-“when” in mice might be useful in the search for the neural substrates of episodic memory, the screening for promnestic drugs and the behavioral phenotyping of genetic models of neuropsychiatric diseases affecting episodic memory.

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小鼠的情景样记忆:同时评估对象、地点和时间顺序记忆
情景记忆指的是有意识地回忆一段独特的过去经历,包括“发生了什么”、“在哪里”和“何时”发生。由于情景记忆缺陷在许多神经精神疾病(如阿尔茨海默病)中发现,并且有几种药理学、病变和遗传动物模型可供使用,因此需要情景样记忆的动物模型,以便用于设计适当的治疗方法。然而,即使把动物有意识回忆的问题排除在外,情景记忆在非人类哺乳动物身上也很难得到证明,因为还不可能证明对“什么”、“在哪里”和“什么时候”有完整的记忆。我们设计了一个“什么”、“在哪里”和“什么时候”的对象探索任务,其中将不同版本的新颖性偏好范式结合起来,包括(a)对象识别记忆,(b)对对象探索位置的记忆,以及(c)在不同时间点呈现的对象的时间顺序记忆。我们的研究结果表明,小鼠能够(a)识别以前探索过的物体,(b)记住以前遇到过特定物体的位置,(c)区分不同物体出现的相对时间。我们认为,我们的方案提供了同时评估对象记忆的“是什么”,“在哪里”和“何时”,在寻找情景记忆的神经基质,筛选促梦药物和影响情景记忆的神经精神疾病遗传模型的行为表型方面可能是有用的。
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