Mechanisms of configural learning in a rat model of FASD

University Of Delaware, Newark DE

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Abstract

DESCRIPTION (provided by applicant): Fetal Alcohol Spectrum Disorder (FASD) is a leading cause of intellectual and developmental disabilities that continues to be a significant medical and societal problem in the U.S. and around the world. Neuroanatomical and behavioral abnormalities commonly seen in FASD include deficits in hippocampus- dependent learning and memory. We have recently shown that a test of configural/spatial information processing---the context preexposure facilitation effect (CPFE)---is unusually sensitive to various doses and developmental windows of alcohol exposure in a rodent model of FASD. The proposed research seeks to characterize these behavioral deficits and explore interventions that reverse the deficits in a manner that informs underlying neurobiological mechanisms. The CPFE is a variant of contextual fear conditioning in which learning about the context, consolidation of the context memory, associating the context memory with shock, and retrieval of the context-shock association each require normal functioning of the hippocampus. Notably, each of these processes occur during separate phases of the CPFE procedure, making them amenable to experimental manipulations that can reveal which processes are disrupted by neonatal alcohol exposure and which are subject to neuropharmacological intervention. Aim 1 will determine whether ethanol-induced deficits in the CPFE reflect impaired encoding and consolidation of configural/spatial representations and/or other component processes. Aim 2 will determine whether increasing cholinergic function with intrahippocampal infusions of physostigmine can reverse these ethanol-induced deficits and/or deficits in other component processes underlying the CPFE. Aim 3 will determine whether impairment of the CPFE by neonatal alcohol exposure is associated with reduced early growth gene 1 (EGR-1) expression in hippocampus or amygdala during the preexposure or training phases of the CPFE. The proposed research is significant because it is directed at an important public health problem and because it is likely t advance basic research on FASD.