The projects in this Center explore the molecular and morphologic basis of aging in pyramidal cells in theprefrontal cortex, neurons that play a critical role in working memory function. The mission of the Histologyand Morphometry Core is to process brain tissue in a manner that is suitable for quantitative analysis ofdendritic 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 neuronaltracing with the Neurolucida system and photoimaging of dendrites on the confocal microscope. For Golgiimpregnation, we have chosen to use the FD Rapid GolgiStainTM kit as this method represents a synthesisof the Golgi-Cox and rapid Golgi techniques, exploiting the advantages of both methods to optimize thequality of impregnated somata and dendritic spines. Golgi-impregnated pyramidal neurons in layer III will betraced with the aid of a computer-integrated microscopy system (Microbrightfield, Williston, VT) featuringNeurolucida software. Measurements of linear spine density, dendritic length and dendritic complexity (Shollanalysis) will be derived from tracings for between-group comparisons, e.g., aged vs. young rats. Sliceinjection and intracellular filling of pyramidal neurons with LY will confirm the findings from Golgi analysesand provide a complete 3D reconstruction of dendritic spines on selected dendritic segments via confocalmicroscopy. Dr. Patrick Hof, Mount Sinai School of Medicine, will lend his expertise as a consultant for theLY injections and analyses. Brain tissue from rats and monkeys studied in Projects 2-4 will be processed andanalyzed by the Core. Our goals are to provide histologic processing of uniformly high quality and to collectdata in a systematic and consistent manner across the experimental designs of individual projects. In sodoing, 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: Decliningmemory and cognitive function are generally regarded as inevitable and intractable consequences of thenormal aging process in human populations. Understanding the underlying structural and molecular basis ofthe age-related deficits in mental capacity and exploring the potential reversibility of dendritic atrophy maylead to prophylactic treatments that preserve mental functioning in elderly subjects.
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