The denate gyrus of the hippocampus is an area where new neurons continue to be generated throughout adult life. Although the role of adult hippocampal neurogenesis is still debated, accumulating evidence suggests that it is involved in the acquisition of certain forms of hippocampal-dependent learning. Based on those findings, we have begun to explore the relationship between learning deficits and neurogenesis in adult offspring of prenatal ethanol exposed rodents. For these studies, we have utilized a mouse model of fetal alcohol exposure (FAE) that is based on free-choice and represents a moderate alcohol access model of FAE. Adult offspring of FAE mice display learning deficits similar to that of the FAE rat, but the FAE mouse model is not confounded by potential diet and pair feeding effects. Preliminary data presented in this proposal demonstrate that FAE does not impair basal neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment. Studies outlined in this exploratory R21 proposal are designed to determine a) whether FAE also impairs the neurogenic response to hippocampal-dependent learning, and b) whether mitigation of the neurogenic response to behavioral challenge is due to intrinsic defects of FAE progenitors and/or due to microenvironmental changes within the neurogenic niche of the adult SGZ. Our preliminary studies are among the first to demonstrate that prenatal exposures can result in persistent defects in adult hippocampal neurogenesis. Since learning disabilities are among the most prevalent and pervasive fetal alcohol-related defects in children, further studies to understand the basis of these deficits in animal models of prenatal ethanol exposure seems warranted.
