An understanding of the fundamental cognitive and neural processing mechanisms underlying higher order memory depends critically on animal models of human amnesia, yet the development of a valid animal model has not been fully realized because of differences in conceptualizations of memory processes and experimental approaches to the study of memory in humans and animals. In our view these differences can be bridged with a comparative neuroscience approach.
Our aim i s to continue to develop a rodent model of memory capacities heretofore generally recognized only in humans by identifying cognitive processes that characterize both human and animal memory performance. At the same time, our perspective addresses evolutionary differences in the expression of memory in the animals and humans by exploiting the superb olfactory learning and memory capacities of rodents. If successful our approach may lead to modifications in memory assessments aimed towards understanding, and ultimately , treating disease associated with dysfunction of the hippocampal system, including Alzheimer~s disease, schizophrenia, and autism. Guided by current theoretical conceptions of human amnesia, we will develop new behavioral paradigms that dissociate impaired and preserved learning and memory capacities in animals with hippocampal system damage. In the initial funding period we have successfully shown that the hippocampus is critical to the organization of memories according to relevant relations among the items in memory and to flexible memory expression across a broad scope of learning materials, consistent with characterizations of declarative memory dependent on the hippocampal region in humans. Furthermore, we have demonstrated that anatomically distinct components of hippocampal system subserve different roles in memory processing. The proposed experiments will serve to further specify this characterization of hippocampal memory processing. So far, our research has focused on hippocampal function in mediating the organization of information according to associations or logical relations among the items independent of when the information was obtained. The proposed studies are aimed to determine whether the hippocampal system also mediates the acquisition of flexible expression of temporally organized material. Furthermore, we will characterize the role of hippocampal structures in memory for unique events, by assessing memory performance across a range of tasks involving different types of learning materials and different demands for flexible memory expression. In addition, we will examine the phenomenon of memory consolidation, determining which hippocampal structures are required for permanent memory storage and exploring the link between hippocampal processing of stimulus relations and mechanisms of consolidation. Finally, we compare the effects of different types of damage to the hippocamapal system. In addition, we will test specific hypotheses about the distinct roles of the hippocampus and parahippocampal region, and about potential specializations of the dorsal and vental hippocampus and of the perirhinal and postrhinal cortex.
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