This grant proposal is targeted at furthering the training and research skills of the applicant in the field of alcohol research, specifically Fetal Alcohol Spectrum Disorders (FASDs). The training portion of this proposal will coincide with the majority of the research plan in that the applicant will be learning many of the techniques for the first time, as well as fostering her abilities to effectively communicate her research and findings to her colleagues. The research plan is rooted in the medical knowledge that moderate ethanol exposure prenatally has been reported to cause behavioral and cognitive deficits in childhood that persist into adulthood. Similar to the behavioral deficits seen in children with a FASD diagnosis, children prenatally exposed to maternal stress have been shown to suffer from learning challenges. The molecular, cellular, and biochemical processes which underlie these disturbances is not well understood. The applicant has developed and characterized a model of combined moderate voluntary prenatal ethanol exposure with a prenatal predator scent exposure as Aim 1 of her dissertation research project. The offspring generated in this model will be used in assessments of the combinatorial effects of dual prenatal insults on learning, as well as measures of activity-dependent changes associated with synaptic plasticity in the dentate gyrus, which comprise Aims 2 and 3 of the project. It is hypothesized that maternal stress during pregnancy will potentiate the learning deficits and diminished activity- dependent changes in synaptic plasticity in the dentate gyrus as seen in moderate prenatal alcohol exposure. In order to assess cognitive abilities and alterations in markers of synaptic plasticity in the dual exposed offspring, two specific aims have been developed in addition to the first specific aim of establishing the model system.
Aim 2, targeted at assessing cognitive deficits in the exposure groups, will use a recently developed, novel Two Trial Trace Conditioning task to assess freezing behavior as a measure of hippocampal sensitive learning. It is expected that the dual prenatal exposure will result in larger cognitive deficits than either the prenatal alcohol or the prenatal stress alone.
Aim 3 is targeted at evaluating changes in markers of synaptic plasticity. The applicant will learn fluorescence in situ hybridization techniques to detect changes in ARC mRNA expression in the dentate gyrus, as well as learn radioligand binding techniques used to detect changes in AMPA receptor expression in the dentate gyrus following learning activation. We expect that the levels of evoked ARC mRNA and AMPA receptor expression will be more reduced in animals exposed to both prenatal alcohol and prenatal stress than animals exposed to either prenatal alcohol or prenatal stress alone. The culmination of this project will result in a novel characterization and an enhanced understanding of the behavioral and biochemical alterations observed in prenatal ethanol and prenatal stress exposed rodents.
Moderate consumption of alcohol during pregnancy and prenatal stress have both been associated with various forms of learning and behavioral deficits in children but the neurobiological basis for these deficits is poorly understood. Research into both prenatal insults has uncovered overlapping effects which indicate that the two insults in combination may interact to impart a more highly deficient outcome than either insult alone. We have developed a research model to evaluate the combined effects of moderate prenatal alcohol consumption and prenatal stress, and studies using this model will characterize the cognitive and biochemical differences in this model system in hopes of better understanding the underlying mechanism of neurological challenge.
