Content area
Healthy cognitive functioning across the lifespan is a societal imperative that requires researchers to understand the brain processes underlying cognition in both normative and diseased states. In this pursuit, animals have been vital in both the testing of novel pharmaceuticals and nonpharmacological therapeutic strategies as well as served as a translational bridge between basic biophysical processes in the brain and higher cognitive function in humans. Frequently, however, insights gained from pre-clinical animal models do not readily translate to the human study participant. While this may be due to a number of reasons, the assertion of the following body of work rests upon the notion that cognitive testing done in animal models is frequently too far removed from the complexities of cognitive problems that humans solve on a daily basis. Enhancing the translational potential of novel interventions aimed at improving cognition therefore necessitates clinically relevant cognitive assays. This dissertation focuses on the automated touchscreen-based task known as Paired-Associates Learning (PAL) in rats, using aging (Chapter 3) and traumatic brain injury (Chapter 4) as models to study how hippocampal network impairment leads to the decline of object-place associative memory. By using a trial-by-trial MATLAB analysis of task performance and strategy selection within a daily session, these chapters aim to provide a detailed look at the specific behavioral deficits that lead to performance decline in these models. Chapter 5 concludes this body of work by focusing on whether activity in the dorsal striatum is related to age-related PAL impairments and overuse of a “response-based” behavioral strategy. Overall, this dissertation documents the decline of object-place associative memory in two models of hippocampal dysfunction while providing novel methods of analyzing behavioral strategy in the PAL task.