Alcohol exposure in the rat over postnatal days (PD) 4-9 causes significant decreases in pyramidal cells in the hippocampus, in addition to causing impaired performance on tasks that depend on the hippocampus. The proposed research will seek to establish a causal link between these neural and behavioral effects, particularly at lower levels of alcohol exposure. The context preexposure facilitation effect (CPFE) offers an ideal preparation to examine the effects of neonatal alcohol on the developing hippocampus. In the CPFE, learning about the context, associating the context with shock, and retrieval of the context memory for behavioral expression occurs on separate days, each of which requires the proper functioning of the hippocampus. We have previously shown that a high binge dose of ethanol over PD4-9 disrupts the CPFE in juvenile rats. Experiment 1 will further explore ethanol-induced deficits during this task by examining the performance of rats subjected to lower doses of developmental ethanol exposure. Experiment 2A will use immunohistochemistry techniques to explore the molecular basis of contextual fear conditioning during the CPFE paradigm by examining immediate early gene expression (Fos &Arc protein) in the hippocampus during the three phases of the CPFE paradigm in (undisturbed) control rats. Using the behavioral and immunohistochemical techniques of the preceding experiments, Experiment 2B and 2C will examine how possible molecular aberrations in the hippocampus and the amygdala, respectively, may contribute to the behavioral deficits in the CPFE seen in rats exposed to a low and high dose of ethanol over PD4-9. PUBLIC HEALTH RELEVANCE: Fetal Alcohol Spectrum Disorders (FASD) represent a range of neurobehavioral and structural disorders caused by developmental alcohol exposure, and constitute one of the leading preventable causes of mental retardation. Despite public awareness programs prevalence of FASD remains around 10 per 1,000 births. Animal model research has greatly increased our understanding of how the pattern, level, and developmental period of alcohol exposure influences neurobehavioral outcome;and is helping to identify mechanisms of brain injury and guiding the development of effective treatments for FASD. The research in this proposal addresses an important and continuing challenge for animal model research, which is to demonstrate neurobehavioral effects and mechanisms at lower doses of alcohol exposure that are adverse in humans but often less so in animals.