Adult Neurogenesis, Regulation and Potential Function

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For most of the 20th century, the adult brain was thought to lack the neural plasticity seen in young brains and, particularly, to be incapable of generating new neurons. This perspective is falling from favor, as one of the most exciting areas of biological research is the study of adult neurogenesis - the proliferation and differentiation of neuronal progenitor cells. Researchers have recently suggested that the regulation of neurogenesis in adult humans is important in the physiology or pathophysiology of many processes, including cognition, affect, and aging (to name a few). Such avenues of research are likely to become increasingly prominent in biomedical research, but the significance of naturally occurring neurogenesis in adults of any species remains unknown. While neurogenesis in adult songbird brains appears to support seasonal cycles of song learning and memory, the definitive studies remain elusive. The current studies will take advantage of the relatively simple brain of the bullfrog, Rana catesbeiana, to enhance our knowledge of this complex process. We will combine field studies, primary cell culture, and double-labeling using laser confocal microscopy to investigate the fate of cells born in adult frog brains, attempt to identify regulatory mechanisms, and address the potential significance of adult neurogenesis from the perspective of neuroendocrine cells rather than complex behaviors. Specifc aims are to: 1) Characterize the distribution and extent of cell proliferation and the fate of newly generated cells in adult bullfrog brains; 2) Investigate seasonal and sex differences in cell proliferation and/or cell survival; 3) Characterize the proliferation, differentiation and identity of ependymal progenitors in primary culture; 4) Test the hypothesis that stress hormones alter cell proliferation, differentiation or survival; 5) Test the hypotheses that two neurochemicals that may regulate neurogenesis in mammals, serotonin and brain-derived neurotrophic factor, regulate neurogenesis in amphibians; 6) Begin investigating the potential significance of adult neurogenesis by testing the hypothesis that cell proliferation in the preoptic area and hypothalamus leads to generation of cells with known neuroendocrine functions. All the preliminary data presented in this proposal have been obtained by a group of undergraduate researchers representing diverse ethnic, age and socioeconomic groups, and a major goal of these studies is to continue providing opportunities for undergraduate and graduate student research. More than an opportunity to participate in cutting edge neuroscience, research in adult neurogenesis is intrinsically interesting to scientists and the media, making it a wonderful topic for developing student's critical reasoning skills.