The purpose of this program project is to study behavioral and brain function from the intrauterine period through 120 days in rats whose mothers had been malnourished by subjecting them to a diet of moderate protein restriction, both prior to and throughout pregnancy. The program will make use of a model developed in our laboratory in which the offspring of rats fed a 6% casein diet show impaired brain function despite adequate rates of postnatal growth. These rats will be compared with the offspring of rats fed a 25% casein diet on which optimal physical and brain growth occur. An important and unique contribution of the program project will be the interdisciplinary research by the Behavior, Neurophysiology, Neuroanatomy, and Molecular Neurobiology Divisions in the same animal model in order to identify mechanisms underlying observed brain and behavioral deficits. This will be undertaken by emphasis on the hippocampal formation and its inputs which are known to be sensitive to a range of environmental insults. All divisions will explore the hypothesis that prenatal malnutrition enhances the inhibitory process in the hippocampal formation due to alterations in the GABA system. Accordingly, we plan to challenge the central nervous system and during later development, using drugs activating at the BZ/GABAa complex and exposure to stress, to compromise any compensatory adaptation in brain structure or function which may have occurred secondary to malnutrition. This area of investigation has considerable relevance for humans because of the documented long-term effects of early childhood malnutrition during periods of rapid brain growth on later mental development and the widespread prevalence of this condition both in developing regions of the world and in the U.S.
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