M.D. (co-PI)
Oregon Health and Science University
PI Award ID: 

Aging is often associated with declining cognitive function. This decline could conceivably be prevented if it was possible to replace old neurons with new ones. In a region of the brain called the hippocampus, this actually occurs and newborn neurons continue to be generated into adulthood. These neurons ultimately integrate into pre-existing circuits where they participate in certain learning and memory processes. Adult hippocampal newborn neuron production is exquisitely sensitive to spatial learning tasks, exposure to enriched environments, and physical exercise. These stimuli also cause extensive maturational changes in this population of cells that can persist for months. Blocking adult hippocampal newborn neuron production impairs performance of mice in complex spatial learning paradigms, and it has been suggested that the diminishment in production of these newborn neurons in human aging could contribute to cognitive decline. Newborn neuron proliferation begins to decline at 1-2 months of age in mice and is barely present in aged animals. Remarkably, simple interventions, such as physical exercise, increase the production, maturation, and function of these neurons in a way that could be beneficial for health and well being. How stimuli such as exercise influence hippocampal neurogenesis, whether their positive effects continue into old age, and whether the resultant changes are beneficial remain largely unknown. This proposal utilizes a new method to monitor the transcriptional properties of adult newborn hippocampal neurons as they transition from neuronal progenitors to fully mature components of existing functional circuits and, finally, to cells that have experienced the ravages of old age. Our studies will provide the first glimpses into the transcriptional changes that occur with aging in a select population of neurons within living mice and may uncover mechanisms that permit these cells to respond to exercise and other environmental stimuli.