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.

Public Health Relevance

The proposed project will impact public health by establishing innovative new approaches to better understand the ontogeny of hippocampus-dependent memory, and determining whether processes of acquisition vs. expression contribute to the relatively late emergence of trace fear conditioning. The proposed project will advance both basic animal research and clinical practice directed at a broad range of developmental neurobehavioral disorders involving abnormal maturation of the hippocampus. By elucidating the developmental timing of acquisition vs. expression of cognitive function, the proposed research could cause assessment of, and interventions for, impaired cognitive development to occur earlier in ontogeny (when information is acquired) than is typical of current practices (which wait until stages of development when information is expressed). Finally, this application will advance public health via its translational application to ongoing research on rodent models of Fetal Alcohol Spectrum Disorder (FASD). If successful, it will help this ongoing research identify the developmental and neural mechanisms through which alcohol impairs cognitive development and through which nutritional or experiential interventions improve behavioral outcome.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Freund, Lisa S
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University of Delaware
Schools of Arts and Sciences
United States
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Robinson-Drummer, Patrese A; Dokovna, Lisa B; Heroux, Nicholas A et al. (2016) Cholinergic mechanisms of the context preexposure facilitation effect in adolescent rats. Behav Neurosci 130:196-205
Ramsaran, Adam I; Sanders, Hollie R; Stanton, Mark E (2016) Determinants of object-in-context and object-place-context recognition in the developing rat. Dev Psychobiol 58:883-895
Ramsaran, Adam I; Westbrook, Sara R; Stanton, Mark E (2016) Ontogeny of object-in-context recognition in the rat. Behav Brain Res 298:37-47
Robinson-Drummer, Patrese A; Stanton, Mark E (2015) Using the context preexposure facilitation effect to study long-term context memory in preweanling, juvenile, adolescent, and adult rats. Physiol Behav 148:22-8
Hamilton, G F; Jablonski, S A; Schiffino, F L et al. (2014) Exercise and environment as an intervention for neonatal alcohol effects on hippocampal adult neurogenesis and learning. Neuroscience 265:274-90
Westbrook, Sara R; Brennan, Lauren E; Stanton, Mark E (2014) Ontogeny of object versus location recognition in the rat: acquisition and retention effects. Dev Psychobiol 56:1492-506
Schreiber, W B; Asok, A; Jablonski, S A et al. (2014) Egr-1 mRNA expression patterns in the prefrontal cortex, hippocampus, and amygdala during variants of contextual fear conditioning in adolescent rats. Brain Res 1576:63-72
Jablonski, S A; Stanton, M E (2014) Neonatal alcohol impairs the context preexposure facilitation effect in juvenile rats: dose-response and post-training consolidation effects. Alcohol 48:35-42
Asok, Arun; Schreiber, William B; Jablonski, Sarah A et al. (2013) Egr-1 increases in the prefrontal cortex following training in the context preexposure facilitation effect (CPFE) paradigm. Neurobiol Learn Mem 106:145-53
Jablonski, S A; Schreiber, W B; Westbrook, S R et al. (2013) Determinants of novel object and location recognition during development. Behav Brain Res 256:140-50

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