Discrimination of What, Where, and When

点击翻译按钮获取中文摘要

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.