Mechanisms of Trace Fear Conditioning in the Developing Rat

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DESCRIPTION (provided by applicant): This R21 exploratory grant application will study a largely neglected and poorly understood principle of the ontogeny of learning---acquisition vs. expression---that will likely yield new insights into the development and neural basis of hippocampus-dependent memory. Research on acquisition vs. expression of delay fear conditioning during ontogeny has yielded novel and unanticipated insights concerning how the amygdala and specific efferent pathways cooperate to generate learned fear. However, other developmental research with other types of learning indicates that acquisition occurs first and expression of this learning emerges later in development. To explore these two possibilities in the case of hippocampus-dependent learning, Drs. Mark Stanton and Jeff Rosen at the University of Delaware; and Dr. Pam Hunt at the College of William and Mary will use behavioral, molecular and neuropharmacological approaches to study acquisition vs. expression of trace fear conditioning in developing rats. In Aim 1, two studies in the Hunt laboratory will explore the role of acquisition vs. expression of learning in the ontogenetic emergence trace conditioning between postnatal day (PD) 23 and PD28 in the rat. In Aim 2, immediate-early-gene expression assays will be performed in the Rosen laboratory on the brains of rats tested behaviorally in Aim 1 to explore the role of developmental differences in neural activity and/or plasticity in hippocampus and amygdala in the ontogeny of trace fear conditioning. In Aim 3, two experiments in the Stanton laboratory will determine the contribution of NMDA- receptor-mediated neural plasticity in dorsal hippocampus to the ontogeny of acquisition vs. expression of visual trace conditioning in PD23-28 rats. This project is innovative because it will be the first to examine acquisition vs. expression of hippocampus-dependent learning during ontogeny using an integrated, multidisciplinary approach. If successful, it will yield novel and important insights that would be pursued more thoroughly in subsequent R01 applications. The project is also significant because it will advance the study of developmental disorders involving aberrant maturation of the hippocampus. For example, Dr. Hunt's laboratory has shown that trace fear conditioning is an especially sensitive outcome measure for studying adverse cognitive effects of developmental alcohol exposure. However, understanding of the neural mechanisms of these effects is hampered by a lack of information on brain-behavior relationships mediating trace conditioning during this period of development. This R21 project seeks to fill that gap. Finally, this project will establish a new multi-investigator collaboration that has strong potential to advance these and other important issues in the developmental neurobiology of learning.