Prenatal ethanol exposure effects on NMDA receptor localization and function

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DESCRIPTION (provided by applicant): The training program outlined in this grant application was specifically designed for the applicant with focuses on the acquisition of multi-disciplinary research skills and professional development. The research component of the training program will investigate neurochemical mechanisms that underlie the damaging effects of developmental exposure to alcohol in a mouse model of prenatal alcohol exposure (PAE). PAE is associated with a range of physical, cognitive and behavioral abnormalities in both human populations, where it is termed fetal alcohol spectrum disorder (FASD), and in animal models. In animal models, PAE has been shown to exert effects on multiple brain structures and functions that are important in cognition, including the N-methyl- D-aspartate (NMDA) receptor (NMDAR). The proposed research studies will employ biochemical and electrophysiological techniques to examine the distribution and properties, respectively, of NMDARs in the mouse dentate. Damage to the dentate gyrus during development may have long-lasting and far-reaching consequences since this structure serves as a major cortical input pathway into the hippocampus. It is hypothesized that PAE leads to an increased presence of NR1/NR2A-containing NMDA receptors in the extrasynaptic membrane of the dentate gyrus, and this is associated with an increase in NMDA-dependent activity in the extrasynaptic compartment. If such an increase does exist, it will provide a novel target for therapeutic intervention in the treatment of cognitive dysfunctions in FASD. PUBLIC HEALTH RELEVANCE: Prenatal exposure to alcohol causes a multitude of life-long physical, behavioral, cognitive and social abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). The research component of the proposed training program aims to increase our knowledge of neurochemical mechanisms that underlie the damaging effects of prenatal alcohol exposure on learning and memory. A better understanding of these mechanisms will assist in the development of novel therapies that could improve treatment outcomes for those afflicted with FASD.