The projects in this Center explore the molecular and morphologic basis of aging in pyramidal cells in the prefrontal cortex, neurons that play a critical role in working memory function. The mission of the Histology and Morphometry Core is to process brain tissue in a manner that is suitable for quantitative analysis of dendritic arborization and spine density, i.e., Golgi impregnation and Lucifer Yellow (LY) intracellular filling. The Core is also responsible for application of quantitative neuroanatomic methods, specifically neuronal tracing with the Neurolucida system and photoimaging of dendrites on the confocal microscope. For Golgi impregnation, we have chosen to use the FD Rapid GolgiStainTM kit as this method represents a synthesis of the Golgi-Cox and rapid Golgi techniques, exploiting the advantages of both methods to optimize the quality of impregnated somata and dendritic spines. Golgi-impregnated pyramidal neurons in layer III will be traced with the aid of a computer-integrated microscopy system (Microbrightfield, Williston, VT) featuring Neurolucida software. Measurements of linear spine density, dendritic length and dendritic complexity (Sholl analysis) will be derived from tracings for between-group comparisons, e.g., aged vs. young rats. Slice injection and intracellular filling of pyramidal neurons with LY will confirm the findings from Golgi analyses and provide a complete 3D reconstruction of dendritic spines on selected dendritic segments via confocal microscopy. Dr. Patrick Hof, Mount Sinai School of Medicine, will lend his expertise as a consultant for the LY injections and analyses. Brain tissue from rats and monkeys studied in Projects 2-4 will be processed and analyzed by the Core. Our goals are to provide histologic processing of uniformly high quality and to collect data in a systematic and consistent manner across the experimental designs of individual projects. In so doing, the Core will facilitate integration of data among projects and further the overall goal of the Center, i.e., to understand the structural basis of age-related cognitive dysfunction. LAY SUMMARY: Declining memory and cognitive function are generally regarded as inevitable and intractable consequences of the normal aging process in human populations. Understanding the underlying structural and molecular basis of the age-related deficits in mental capacity and exploring the potential reversibility of dendritic atrophy may lead to prophylactic treatments that preserve mental functioning in elderly subjects.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1)
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Yale University
New Haven
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