A novel paradigm to investigate memory reconsolidation in adult and aged rats

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DESCRIPTION (provided by applicant): Reconsolidation is the process by which memories which have become unstable due to re-instantiation (remembering) are re-stabilized. During this process, new information can become incorporated into old memories. Because reconsolidation is a fundamental phase of memory processing, deficits in reconsolidation could partially account for impairments in episodic memory associated with aging and various memory disorders. The long-term goals of the proposed research are to determine the network mechanisms by which memory reconsolidation occurs and to assess if and how these mechanisms change with aging. The objectives of this proposed study are to study reconsolidation of positively motivated spatial memory in both young and aged rats and to investigate the neural substrate associated with reconsolidation. In order to fulfill these objectives, three specific aims will be addressed. (1) The first aim is to investigate the effect of experimental context on reconsolidation of positively motivated spatial memories. To pursue this aim, adult rats will be trained on Day 1 to run to 3 different feeders (List 1) for sugar water reward. On Day 2, rats will be trained to run to 3 different feeders (List 2) in either the same or a different experimental context than that used on Day 1. On Day 3, rats must recall List 1, and reconsolidation will be measured as the percent of incorrect visits made to List 2 feeders. (2) The second aim is to measure the extent to which post- task replay of neural activity reflecting List 1 and List 2 memory items correlates with the errors made by the animals during memory recall. To pursue this aim, extracellular activity in area CA3 of the hippocampus will be recorded in adult rats as they perform a condensed version of the behavioral task described above. (3) The third aim is to measure memory reconsolidation in aged animals. To pursue this aim, the behavioral experiment described above will be conducted with aged rats. This research will provide a new animal model for memory reconsolidation, insights into its neural mechanisms, and the first data illustrating how this process may change with age, thus shedding light on the dynamic nature of memory and age-related memory impairment. PUBLIC HEALTH RELEVANCE: Relevance to public health: Memory impairments are associated with aging and characterize various cognitive disorders, such as dementia and post-traumatic stress disorder. Studying the process by which memories are maintained and updated after recollection and how this process changes with age will contribute to a better understanding and, ultimately, prevention and treatment of such memory deficits.