Mechanisms for Environmental and Genetic Reversal of Gender Biased Behavior

描述（由申请人提供）：性与行为之间的关系是一个来自社会，以及医学界和研究界的持久问题。神经科学研究无可否认地表明，个体的遗传性别对大脑解剖区域和行为都有广泛的影响。然而，平行的研究表明，仅基于基因组序列预测表型是不准确的，因此暗示了环境的影响。我建议对比遗传和环境对性别偏见行为的影响机制，使用一对结合的亲代照顾的一夫一妻制动物模型，朱丽多色属，非洲慈鲷鱼。我采用了“系统生物学”的方法，定量地整合了来自多个水平的表型数据，包括神经基因表达、激素滴度和行为观察。非洲慈鲷提供了一个独特的机会来观察自然行为，其中性别偏见行为可以通过环境影响或遗传影响来逆转。因此，行为表型、激素水平和基因表达谱可以通过以下三种范式进行评估：1)传统的性别角色2)环境逆转3)基因逆转。在传统的性别偏见范式中，雄性体型更大，更具攻击性和领地意识，而雌性则负责照顾卵子和维护巢穴。在同一物种中，改变社会环境会逆转性别偏见行为，而在一个密切相关的物种中，性别偏见行为会因遗传背景而逆转。跨多个表型水平的协方差分析将确定与独立于性别的性别偏见行为相关的分子模块。范式1将被用作测量和对比两种逆转表型的基线，范式2和范式3中招募的分子模块将被对比，以评估环境和遗传影响的机制。性别偏见神经元基因表达的定位将指出调节这些行为的神经解剖学位点，从而为解决协调可塑性和偏见性别角色行为的神经和分子网络关系的模型系统奠定基础。在神经解剖学、神经化学、脑功能甚至行为层面上，性别对大脑的巨大影响是不可否认的。系统水平的研究整合了行为、生理和分子水平的数据，以对比基因和环境影响性别偏见行为的机制，并确定对这些行为的调节重要的神经解剖学位点。我使用动物模型（慈鲷鱼）来研究复杂的社会行为，这些行为与人类社会行为中广泛的正常性别相关差异以及显示遗传和环境因素的精神状况直接相关。

DESCRIPTION (provided by applicant): The relationship between sex and behavior is a persistent question from society, as well as the medical and the research communities. Neuroscience research has undeniably demonstrated that the genetic sex of an individual has broad ranging effects on both anatomical brain areas and behaviors. However, a parallel line of research has demonstrated the inaccuracy of predicting phenotype based solely on genome sequence, thus implicating environmental influence. I propose to contrast the mechanisms that underlie genetic and environmental influences on gender biased behaviors using a pair-bonded monogamous animal model of parental care, genus Julidochromis, African cichlid fishes. I take a "systems biology" approach that quantitatively integrates phenotype data from multiple levels including neural gene expression, hormone titers, and behavioral observations. The African Cichlid fishes provide a unique opportunity to observe naturalistic behaviors in which gender-biased behaviors can be reversed by either environmental effects or genetic effects. The behavioral phenotypes, hormone levels, and gene expression profiles can therefore be assessed in these three paradigms 1) conventional gender-role 2) environmental reversal 3) genetic reversal. Within the conventional gender-bias paradigm the males are larger, more aggressive and territorial, while the females provide the egg care and nest maintenance. In this same species, altering the social environment, will reverse gender-biased behaviors, while in a closely related species the gender-biased behaviors are reversed by genetic background. Covariance analysis across multiple levels of phenotype will identify molecular modules that correlate with gender biased behaviors independent of sex. Paradigm 1 will be used as baseline from which to measure and contrast the two reversal phenotypes, and the molecular modules that are recruited in paradigms 2 & 3 will be contrasted in order to evaluate the mechanisms that underlie environmental and genetic influence. The localization of gender-biased neuronal gene expression will indicate neuroanatomical sites for regulation of these behaviors and thus lay the foundation for a model system in which to address the relationship of neural and molecular networks that orchestrate plastic and biased gender-role behavior. PUBLIC HEALTH RELEVANCE The great influence of sex on the brain is undeniable at the level of neuroanatomy, neurochemistry, brain function, and even behavior. The proposed systems level research integrates data from behavioral, physiological and molecular level in order to contrast mechanisms by which genes and the environment influence gender-biased behaviors and identify neuroanatomical sites important for the regulation of these behaviors. I use an animal model (cichlid fish) to study complex social behaviors that are directly relevant to the broad range of normal sex-related differences in human social behaviors as well as psychiatric conditions that show both genetic and environmental components.