Discrimination of What, Where, and When

描述（由申请人提供）：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。本应用程序的目的是确定大鼠区分什么、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的人类记忆病理中，记忆内容（关于事件发生的时间、地点和内容的记忆）的损伤非常突出。中心假设是，大鼠的时间间隔相对于重要的早期事件来区分什么，在哪里，什么时候。PI将通过实现两个具体目标来检验中心假设：确定重访策略用于区分什么，在哪里，什么时候。可行的假设是，老鼠通过学习具体的“什么-什么”偶然性来解决对“什么”、“地点”和“时间”的区分。这一假设将通过训练老鼠辨别什么、在哪里、什么时候使用两种“什么-什么”偶然事件（即，两种支配两种不同味道补充的偶然事件）来验证。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、地点和时间时，在重要事件（例如，研究和测试阶段）之间的时间间隔。因此，研究间隔时间的标准心理物理学方法将被用于研究与区分什么、地点和时间有关的时间机制。这一假设将通过(1)获得泛化梯度，(2)检查时间变异性的标量特性，以及(3)确定时间、地点和时间的时间重置机制来验证。人类情景记忆的缺陷是对事件发生的内容、地点和时间的记忆缺陷（即情景记忆的内容）。因此，研究动物对什么、在什么地方、什么时间的辨别，对于理解人类记忆障碍具有巨大的潜力。该项目与健康的关系包括确定控制对什么、在哪里、何时理解记忆障碍的歧视的机制。这种类型的基础研究为精神和行为障碍的性质和起源提供了新的见解，这可能最终影响未来研究中改进治疗方法的发展。因此，拟议的研究将确定在大鼠中辨别什么、在哪里、何时的行为机制，以促进我们对认知的基本方面的理解，这些方面可能在精神障碍中变得功能失调。这种行为机制的识别对于促进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的未来进展至关重要，最终目标是确定这些系统的异常如何引起精神疾病。公共卫生相关性：研究控制记忆的基本机制是一项迫切的公共卫生需求，因为记忆障碍，如阿尔茨海默病和其他常见的人类记忆病理，给社会带来了重大的社会经济负担。对事件发生的内容、地点和时间的记忆缺失与记忆障碍有关。因此，研究动物对什么、在什么地方、什么时间的辨别，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.