The brain continues to generate new neurons in the hippocampus throughout adulthood. The process of neurogenesis is influenced by environmental factors such as learning, stress, spatial complexity, and physical activity. The proposed research will explore the control of neurogenesis by wheel running activity, and investigate the temporal and physiological parameters of this phenomenon. In addition, the volitional aspect of exercise will be examined using forced treadmill and voluntary running wheel activity. The thymidine analog 5-bromodeoxyuridine (BrdU) is typically used in studies of cell proliferation and survival in the hippocampus. However, when studying environmental factors that elevate the circulatory system, the issue of availability causes difficulty in interpretation of results. To this end, immunolabeling for the endogenous markers Ki-67 and phospho-histone H3 will be applied to provide a measure of exercise-induced neurogenesis that is not affected by systemic elevation. Physical activity has been correlated with a lower incidence of dementia in older adults, and the data from studies of exercise-induced neurogenesis may one day be applied to the prevention or treatment of neurodegenerative disease. ? ?