Cells proliferate in the inner granular zone of the dentate gyrus of the adult hippocampus of all mammals. It is hypothesized that some of the dividing cells are stem cells because they can give rise to neurons and glia in the dentate gyrus. Additionally, we have demonstrated that cells from the adult hippocampus can be isolated in vitro and induced to proliferate indefinitely. Under specific conditions the cells can be transplanted back into the adult brain where they can differentiate into neurons and glia. We demonstrated previously that there is a progressive decrease in the number of proliferative cells in the dentate gyrus of adult rodents with aging. This decrease in neurogenesis in the aged dentate gyrus can be partially reversed by environmental stimulation. We do not know whether newly born cells in the aged brain can become neurons that are anatomically and functionally similar to the new neurons in the young adult brain. Further, we do not know if environmental stimulation like voluntary exercise will affect only the proliferation rate and survival of the newly born neurons, or whether it will also affect the anatomical or physiological properties of the differentiated cells. To determine the answer to these questions in vivo we developed new methods that allow us to measure anatomical and physiological properties of individual, newly born cells in acute brain slices. Further, we developed methods to isolate adult stem cells in vitro and measure their functional and electrophysiological properties in vitro. Finally, using transplantation methods established in this lab we can directly compare the effects of the age of the host hippocampus on survival and function of grafted aged versus young adult stem cell populations propagated in vitro.
