The proposed project will extend current knowledge on how aging affects the structure of the rat hippocampal formation - a well-characterized brain center known to function in memory acquisition and retrieval. While there is abundant aging data on the dentate gyrus in the hippocampus, little is known about anatomical changes in other parts of the hippocampus with regard to aging. Thus, the proposed project will focus on an important hippocampal subfield - area CA1 - in animals aged 3 to 30 months. Using quantitative electron microscopy, a study will determine whether there are age-related changes in the number of synaptic terminals in the stratum lacunosum/moleculare of CA1, which is the site of termination of fibers from entorhinal cortex. To compliment this study, a quantitative light microscopic study will determine if there is an age-related loss of neurons in entorhinal cortex which projects to CA1 and other parts of the hippocampus. In addition, Golgi impregnation studies will be done to determine if there is growth, regression or stability of CA1 pyramidal cell dendrites with advancing age. The project will also focus on the effects of aging on microtubules and microtubule-associated proteins (MAP-2, tau- 1). Thus, quantitative ultrastructural studies will analyze microtubule packing density in the dendrites of CA1 pyramidal cells, and this data will be correlated with ultrastructural studies of microtubule packing density in vitro. Finally, immunocytochemical studies of MAP-2 and tau-1 localization in the aging rat hippocampus will be done, and this data will be correlated with biochemical studies (Project 7) of age-related alterations in MAP-2 and tau-1 activity in the hippocampus. These studies may provide a better understanding of molecular mechanisms regulating neuronal morphology with advancing age.
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