An animal model of parental care: Manipulating social environments with V1aR-RNAi

父母照顾的动物模型：利用 V1aR-RNAi 操纵社会环境

• 批准号: 7658533
• 负责人: STEVEN M PHELPS
• 金额: $ 20.1万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658533
• 关键词: Address; Affect; Animal Model; Animals; Area; Behavior; Behavioral; Biology; Brain; Caregivers; Caring; Child; Child Development; Complex; Data; Data Sources; Development; Distal; Ecology; Environment; Female; Frequencies; Gene Expression; Genes; Genetic; Genome; Globus Pallidus; Heart Diseases; Home environment; Hormonal; Human; Human Development; Mammals; Measures; Methodology; Methods; Modeling; Molecular; Neighborhoods; Neurobiology; Neurons; Neurosciences; Obesity; Outcome; Parents; Partner in relationship; Phenotype; Physiology; Predisposition; Process; RNA Interference; Research; Research Personnel; Rodent; Rodent Model; Role; Sampling; Schools; Shapes; Social Environment; Socialization; Stress; Techniques; Translating; V1a vasopressin receptor; Vasopressin Receptor; Vasopressins; Work; brain behavior; combination gene therapy; depression; gene therapy; interest; male; nonhuman primate; novel; offspring; parental influence; prairie vole; programs; public health relevance; receptor; relating to nervous system; social; socioeconomics; tool; trait

DESCRIPTION (provided by applicant): Recent attempts to understand the dynamic contributions of genes and environments to human development have emphasized the need to consider environments at different scales; the simplest such distinction is between the immediate home environment and the more distal influences of school, neighborhood, socioeconomics and culture. Rodent species have proved powerful models for investigating the role of these more proximal processes, namely maternal care, on the development of brains and behavior. The examination of how parental care interacts with more distal influences, however, has largely been limited to correlational studies in humans and manipulative studies in non-human primates. Although both sources of data are important, neither provides the capacity for neuronal manipulation present in rodent models. We propose to extend rodent neuroscience into semi-natural settings using a novel combination of gene therapy, RNA interference (RNAi), radiotelemetry and focal video sampling. We outline a research plan that would do so with a unique rodent species, the prairie vole, known for its pairbonding and bi-parental care. We propose to use RNAi methods to manipulate the expression of the vasopressin 1a receptor (V1aR) in the ventral pallidum, a brain area necessary for male pairbonding. We propose to place males with reduced V1aR (V1Ai), control (CONT) males, and unmanipulated females in semi-natural enclosures, with different frequencies of V1Ai and CONT males forming different "neighborhoods." We will then examine the relationship between paternal V1Ai phenotype, social neighborhood, and the parental care received by young. Lastly, we will examine offspring from these nests on measures of stress reactivity, a well-characterized phenotype shaped by parental care in rodents, humans and non-human primates. The resulting data will uniquely address the reciprocal influences of proximal and distal environments on neural and behavioral outcomes. No less importantly, the study will develop methods that address how genomes and social environments interact to influence a broad range of phenotypes. PUBLIC HEALTH RELEVANCE: The interactions between children and their caregivers are critical to child development. Work on rodents has clarified the neuronal and hormonal mechanisms through which care can be translated into lifelong changes in physiology and behavior, including susceptibility to obesity, heart disease and depression. We propose to develop a unique combination of molecular and behavioral tools that would allow researchers to address more complex interactions between social environment, gene expression, and neurobiological and behavioral development.

描述（由申请人提供）：最近试图了解基因和环境对人类发展的动态贡献，强调需要考虑不同尺度的环境;最简单的区别是直接家庭环境和学校，邻里，社会经济和文化的更远影响之间的区别。啮齿动物物种已被证明是研究这些更近端的过程（即母性关怀）对大脑和行为发育的作用的有力模型。然而，对父母照顾如何与更远的影响相互作用的研究，在很大程度上限于人类的相关性研究和非人类灵长类动物的操纵研究。虽然这两种数据来源都很重要，但都不能提供啮齿动物模型中存在的神经元操纵能力。我们建议将啮齿动物神经科学扩展到半自然环境中，使用基因治疗，RNA干扰（RNAi），无线电遥测和聚焦视频采样的新组合。我们概述了一个研究计划，将这样做与一个独特的啮齿动物物种，草原田鼠，其配对和双亲照顾而闻名。我们建议使用RNAi的方法来操纵腹侧苍白球，男性配对所需的大脑区域的血管加压素1a受体（V1 aR）的表达。我们建议将V1 aR降低的雄性（V1 Ai）、对照（CONT）雄性和未被操纵的雌性放置在半自然的围栏中，不同频率的V1 Ai和CONT雄性形成不同的“邻居”。“然后，我们将研究父亲V1 Ai表型，社会邻里和年轻人接受的父母照顾之间的关系。最后，我们将研究这些巢的后代的应激反应的措施，一个良好的特征表型形成的啮齿动物，人类和非人类灵长类动物的父母照顾。由此产生的数据将独特地解决近端和远端环境对神经和行为结果的相互影响。同样重要的是，这项研究将开发出解决基因组和社会环境如何相互作用以影响广泛表型的方法。公共卫生相关性：儿童与其照顾者之间的互动对儿童发展至关重要。对啮齿动物的研究阐明了神经元和激素机制，通过这些机制，护理可以转化为生理和行为的终身变化，包括对肥胖、心脏病和抑郁症的易感性。我们建议开发一种独特的分子和行为工具的组合，使研究人员能够解决社会环境，基因表达，神经生物学和行为发育之间更复杂的相互作用。