Postnatal maturation: A model to study hippocampal aging and Alzheimer's disease

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Project Summary Mounting evidence indicates that adult mental heath status is strongly influenced by the quality of early life care. Abuse, neglect, isolation, and poverty have all been associated with poorer cognitive abilities in adulthood and aging. Moreover, the proportion of the US population that is elderly currently grows at a rapid pace and will reach 20% of the total population by 2030. This translates into a troubling burden on the US health care system to treat aging-related cognitive decline. However, this problem may be at least partially abrogated if rapid action is taken to identify at-risk individuals and create prophylactic interventions. A better understanding of individual risk for memory impairment in adulthood and aging can be gained by knowing how neural systems that regulate memory are assembled during postnatal development. The proposed project is geared toward understanding the spatial memory impairments that are associated with human aging by focusing on the postnatal age in rats when these memory systems are undergoing their final maturation, the end of the third postnatal week. This age in rats parallels the final maturation of spatial memory in humans, which begins at about two to three years after birth. This lifespan-based research design employs assays at the cellular, pharmacological, systems, and behavioral levels. More specifically, the proposed experiments examine changes in the function of fast-acting synaptic glutamate receptors (AMPA receptors) at hippocampal synapses and relationships to alterations in neuronal function and spatial navigation ability. This interdisciplinary project will improve our understanding of memory network maturation, which will aid in understanding the considerable variability in spatial memory abilities in adulthood and aging. Additionally, findings will improve the design of prophylactic measures for memory maintenance and promote more effective treatments for memory impairments in aging.