Epigenetic Influences on Brain and Behavior

描述（由申请人提供）：这是针对NIMH探索/发展补助金（R21）计划的申请。本文描述的这项研究解决了什么决定行为变异及其神经基础的基本问题，特别是婴儿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的性别组成如何改变母性关怀的性质，以及这种早期母性环境如何影响后代成年后的性、攻击性和母性行为的神经基础。目前的建议结合了三名研究人员各自领域的专家的技能（船员：大脑活动的代谢映射;弗莱明：大鼠的性和母性行为;小川：敲除小鼠的攻击性和母性行为），并将以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。拟议研究的总体目标是开发一个创新的研究计划，这将提供一个新的视角和一套技术和方法，将有助于探索基因-环境相互作用，特别是我们的理解如何环境影响基因型和行为之间的关系在敏感的发展时期。有三个具体目标： 具体目标一。检验胎仔的性别和基因型组成会改变产妇护理模式的假设。 具体目标二。为了确定成年后的年轻人的社会性行为是否是由于母亲对她的年轻人的这种差异行为。 具体目标三。为了确定这些动物成年后表现出的不同行为特征是否反映在相互连接的边缘核网络的不同活动模式中。

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.