Peter R Rapp, PhD

Research on the neurology of learning and memory has progressed at a\nremarkable pace over the last twenty years, and our laboratory has capitalized\non this body of evidence to address several inter-related topics. One line\nof research is aimed at establishing a detailed neuropsychological account\nof cognitive aging in the monkey. These studies take advantage of both established\nand newly developed behavioral testing procedures designed to provide a\nwindow on the functional status of brain regions implicated in learning\nand memory. Our accumulated evidence indicates that memory processes dependent\non the prefrontal cortex are particularly susceptible to aging, while the status of memory mediated by the hippocampus and closely related medial\ntemporal lobe structures varies dramatically across individuals. Variability\nin the cognitive effects of aging has attracted considerable attention in\nrecent years, partly because it provides a valuable framework for identifying\nthe neurobiological alterations that are most tightly coupled to age-related\nbehavioral decline. In recent studies of this sort we have demonstrated\nthat hippocampal neuron loss is a less prominent feature of normal aging\nthan previously presumed, and that cell death in the aged hippocampus fails\nto account for the learning and memory impairment observed in a substantial\nproportion of older individuals. Other biomarkers, however, are significantly\ncorrelated with cognitive decline, including hormonal changes and metabolic activity in the aged hippocampus. These findings count against the long-standing\nconcept that frank neuronal degeneration is the proximal cause of behavioral\naging, and instead suggest that cognitive impairment results from functional\nchanges within the surviving architecture of the brain. Receptor systems\nresponsible for learning-related cellular plasticity may play and important\nrole in this regard, and this proposal is currently under investigation\nin collaboration with other members of the Neurobiology of Aging Laboratories.\r\n

A closely related line of inquiry in the laboratory is intended to better\ndefine the specific nature of memory supported by the individual structures\ncomprising the hippocampal system. A central aspect of this project involves\nthe development of new behavioral assessment procedures for the monkey,\nemphasizing precisely those aspects of memory that are thought to critically\ndepend on intact hippocampal function. Utilizing these new tasks, studies\nin young monkeys have begun to examine the effects of selective damage to\nthe hippocampus and associated cortical areas in the medial temporal lobe.\nUltimately, the same procedures should provide valuable tools for establishing\na more complete neuropsychological account of cognitive aging in the monkey,\nand for the rational development of therapeutic strategies for treating cognitive disorders of aging.