Epigenetic Influences on Brain and Behavior

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DESCRIPTION (provided by applicant): This is an application directed toward the NIMH Exploratory/Developmental Grant (R21) program. This research described herein addresses the fundamental question of what determines behavioral variation and its neural underpinnings, in particular the relative roles of genetic and epigenetic factors in infancy in shaping adult brain and behavior. Specifically, this project will examine how the genotype of the offspring and the gender composition of the litter alters the nature of maternal care and how, in turn, this early maternal environment influences the neural underpinnings of sexual, aggressive, and maternal behaviors of the offspring when they become adults. The present proposal combines the skills of three researchers each expert in their respective fields (Crews: metabolic mapping of brain activity; Fleming: rat sexual and maternal behavior; Ogawa: knockout mouse aggressive and maternal behavior) and will utilize two mammalian model systems (knockout mice and the rat) in a new way, thereby developing a novel perspective from which to approach studies of brain organization and behavior. The overall goal of the proposed research is to develop an innovative research program that will provide both a new perspective and a set of techniques and methods that will aid exploration of gene-environment interactions, in particular our understanding of how the environment influences the relationship between genotype and behavior during sensitive developmental periods. There are three specific aims: Specific Aim I. To test the hypotheses that the gender and genotype composition of the litter alter patterns of maternal care. Specific Aim II. To determine if the sociosexual behavior of the young in adulthood are due to this differential behavior of the mother toward her young. Specific Aim III. To establish if the different behavioral profiles exhibited in such animals in adulthood are reflected in different patterns of activity in a network of interconnected limbic nuclei.