Discrimination of What, Where, and When

描述(申请人提供)：长期目标是了解动物如何及时处理事件并记住这些事件，以便为理解记忆障碍提供理论框架。本申请的目的是确定大鼠辨别什么、地点和时间的行为机制。实现这一目标很重要，因为在阿尔茨海默病和其他常见形式的人类记忆病理中，记忆内容--对事件发生的什么、地点和时间的记忆--的损害是突出的。中心假设是，大鼠相对于重大早期事件的时间间隔来区分什么、地点和时间。PI将通过实现两个具体目标来检验中心假设：1.确定用于区分什么、地点和时间的重访策略。工作假设是，大鼠通过学习特定的何时何事偶然事件来解决对什么、地点和时间的辨别。工作假说将通过训练大鼠区分什么、在哪里以及何时使用两个何时何事(即管理两种不同口味的补给的两种意外情况)来检验。2.确定用于区分什么、地点和时间的时间机制。工作假设是大鼠在区分什么、哪里和何时的重大事件(例如，研究和测试阶段)之间的时间间隔。因此，研究间隔计时的标准心理物理学方法将被用来研究区分什么、地点和时间所涉及的时间机制。这一假设将通过(1)获得泛化梯度，(2)检验时间变异性的标量性质，以及(3)在辨别什么、哪里和何时的过程中识别时间重置机制来检验。人类情节记忆缺陷是指对事件发生的内容、地点和时间的记忆缺陷(即情节记忆的内容)。因此，研究动物对什么、什么地方、什么时间的歧视，对于理解人类记忆障碍具有巨大的潜力。该项目的健康相关性包括确定管理对什么、哪里和何时理解记忆障碍的歧视的机制。这种类型的基础研究为对精神和行为障碍的性质和起源的新见解提供了基础，这最终可能会影响未来研究中改进治疗的发展。因此，这项拟议的研究将确定在老鼠身上区分什么、哪里和何时的行为机制，以促进我们对可能在精神障碍中变得功能障碍的认知的基本方面的理解。这种行为机制的识别对于促进未来在理解支持正常认知功能的大脑区域(包括海马体)网络的基本神经生物学方面的进展至关重要，最终目标是确定这些系统中的异常是如何导致精神疾病的。公共卫生相关性：研究管理记忆的基本机制是一项紧迫的公共卫生需求，因为记忆障碍，如阿尔茨海默病和其他常见形式的人类记忆病理，给社会带来了重大的社会经济负担。事件发生的地点、地点和时间的记忆内容缺失与记忆障碍有关。因此，研究动物对什么、何地、何时的区别对于理解人类记忆障碍的神经生物学基础具有巨大的潜力。

DESCRIPTION (provided by applicant): The long-range goal is to understand how animals process events in time and remember these events in order to provide a theoretical framework for understanding disorders of memory. The objective of the present application is to identify behavioral mechanisms by which rats discriminate what, where, and when. Attainment of this objective is important because of the prominence of impairments in the content of memory - memories of what, where, and when an event occurred - in Alzheimer's disease and other common forms of human memory pathology. The central hypothesis is that rats time intervals with respect to significant earlier events to discriminate what, where, and when. The PI will test the central hypothesis by accomplishing two specific aims: 1. To identify the revisit strategy used to discriminate what, where, and when. The working hypothesis is that rats solve the discrimination of what, where, and when by learning specific what-when contingencies. The working hypothesis will be tested by training rats to discriminate what, where, and when using two what-when contingencies (i.e., two contingencies that govern replenishment of two distinctive flavors). 2. To identify the temporal mechanisms used to discriminate what, where, and when. The working hypothesis is that rats time intervals between significant events (e.g., study and test phases) in the discrimination of what, where, and when. Consequently, standard psychophysical methods of investigating interval timing will be used to investigate the temporal mechanisms involved in the discrimination of what, where, and when. This hypothesis will be tested by (1) obtaining generalization gradients, (2) examining the scalar property of temporal variability, and (3) identifying temporal resetting mechanisms in the discrimination of what, where, and when. Deficits in episodic memory in humans are deficits in the memory of what, where, and when events occurred (i.e., the content of episodic memory). Therefore, investigating the discrimination of what, where, and when in animals holds enormous potential for understanding disorders of human memory. The health relatedness of the project includes identifying mechanisms that govern the discrimination of what, where, and when to understand disorders of memory. Basic research of this type provides the foundation for new insights into the nature and origins of mental and behavioral disorders, which may ultimately impact development of improved treatments in future research. Therefore, the proposed research will identify the behavioral mechanisms of the discrimination of what, where, and when in rats to facilitate our understanding of fundamental aspects of cognition that may become dysfunctional within mental disorders. Identification of such behavioral mechanisms is essential to facilitate future progress in understanding the basic neurobiology of the network of brain regions (including the hippocampus) that support normal cognitive function, with the ultimate goal of determining how abnormalities in these systems give rise to mental illness. PUBLIC HEALTH RELEVANCE: The study of basic mechanisms that govern memory is an urgent public health need because disorders of memory, such as Alzheimer's disease and other common forms of human memory pathology, impose a significant socioeconomic burden on society. Deficits in the content of memory for what, where, and when events occurred are implicated in disorders of memory. Therefore, investigating the discrimination of what, where, and when in animals holds enormous potential for understanding the neurobiological bases of human memory disorders.