Deficits in learning and memory in the aged have been observed in aged rodents, non-human primates, and humans. The causes of such deficits are believed to be due to changes in the hippocampus, a limbic structure that is important for the storage and retrieval of various forms of information. To date, little is understood about the morphological changes that may occur in neurons of the hippocampus in the aged, and how such changes could affect cognition. Therefore, the focus of this project is to determine morphological changes in hippocampal CA1 pyramidal neurons in aged rodents and to correlate such findings with performance in a behavioral task that measures learning and memory. The experiments in this study are designed to determine the dendritic lengths and spine densities of CA1 pyramidal neurons in young, older adult, and aged male GFP-expressing transgenic mice. Furthermore, such changes in morphology will be correlated with behavioral assessment in the Morris water maze. The first specific aim will test the hypothesis that an increase in dendritic length occurs in CA1 pyramidal neurons in aged mice as compared to younger age groups. Neurons from the dorsal hippocampus will be digitized in three-dimensions and their dendritic lengths quantified with Neurolucida software. The second specific aim is to test the hypothesis that a decrease in spine density occurs on dendrites on CA1 pyramidal neurons in aged male mice as compared to younger age groups. In addition, spine densities on dendrites from each layer in area CA1 will be compared among the different age groups. The third specific aim is to test the hypothesis that changes in dendritic morphology and spine density will be accompanied by deficits in the Morris water maze, a task that is dependent on the hippocampus. Results from this project will determine if changes in the morphology of individual CA1 pyramidal neurons are correlated with cognitive deficits in the aged. The underlying causes of age-related cognitive deficits are not well understood. There is some suggestion, however, that such deficits could be due to changes in the hippocampus, a limbic structure that is important for the storage and retrieval of various forms of information. Therefore, the focus of this project is to determine morphological changes in hippocampal neurons in aged rodents and to correlate such findings with deficits in learning and memory. ? ? ?
