Unlike most mammalian brain regions which undergo neurogenesis only during a discrete developmental period, the rat dentate gyrus shows cell birth, migration and death well into adulthood. The long term objectives of this proposal are to gain a better understanding of these processes and to determine the factors which regulate their occurrence. Developmental studies have shown that postnatal cell birth, migration and death in the rat dentate gyrus are mediated by adrenal steroids and excitatory amino acid input. Since the adult dentate gyrus retains many developmental characteristics, it is possible that adrenal steroids and/or afferent input continue to regulate these cellular processes throughout the life of the animal. This proposal seeks to determine whether dentate gyrus cell birth, migration and survival are affected in adulthood by those factors which control their occurrence developmentally. In an effort to gain a better understanding of the adult dentate gyrus, the following specific aims will be addressed: 1) to examine the differentiation of newly born cells, 2) to investigate the role that adrenal steroids play in regulating cell birth and survival, 3) to determine whether adrenal steroids regulate the migration of newly born cells, 4) to determine whether dentate gyrus neuroblasts and glioblasts express adrenal steroid receptors, and 5) to determine the role that afferent input plays in the regulation of cell birth and survival. These goals will be achieved by combining in vivo 3H-thymidine autoradiography with immunohistochemistry or retrograde tracing in brains of intact adult rats or adult rats which will be subjected to glucocorticoid manipulations or pharmacological receptor blockade. Cell death is a major contributor to the functional decline seen with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Since most brain regions in the adult do not maintain the ability to create new neurons, cells lost during disease can not be replaced. A better comprehension of a brain region with the unique capacity to generate new cells in adulthood may bring us closer to understanding, as well as influencing, the factors that cause most neuronal populations to lose this ability with time.
