Epigenetic Influences on Brain and Behavior

描述（由申请人提供）：这是一份针对NIMH探索/发展资助（R21）计划的申请。本文所述的研究解决了决定行为变异及其神经基础的基本问题，特别是婴儿时期遗传和表观遗传因素在塑造成人大脑和行为中的相对作用。具体来说，该项目将研究后代的基因型和窝仔的性别组成如何改变母性护理的性质，以及反过来，这种早期母性环境如何影响后代成年后性行为、攻击性行为和母性行为的神经基础。目前的提案结合了三位各自领域专家的技能（Crews：大脑活动的代谢图谱；Fleming：大鼠的性和母性行为；Ogawa：敲除小鼠的攻击和母性行为），并将以一种新的方式利用两种哺乳动物模型系统（敲除小鼠和大鼠），从而开发一种新的视角来研究大脑组织和行为。本研究的总体目标是建立一个创新的研究项目，提供一个新的视角和一套技术和方法，以帮助探索基因-环境相互作用，特别是我们对环境如何影响敏感发育时期基因型和行为之间关系的理解。有三个具体目标：

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.