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Paternal Care, Affiliation and Vasopressin: Mechanisms of Monogamy

父亲的照顾、归属和加压素：一夫一妻制的机制

基本信息

批准号：
8537031
负责人：
Alexander G Ophir
金额：
$ 3.87万
依托单位：
OKLAHOMA STATE UNIVERSITY STILLWATER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8537031
关键词：
Adolescent Adult Affect African American Aggressive behavior Area Argipressin Autistic Disorder Behavior Behavioral Behavioral Research Biological Biomedical Research Brain region Caring Child Development Child health care Complex Conduct Disorder Development Disease Domestic Violence Emotional Environment Exhibits Fathers Fostering Functional disorder Funding Gene Expression Goals Growth Health Health behavior Human Human Development Individual Knowledge Lateral Learning Link Mammals Measures Mediating Mental Health Mission Modeling Neurobiology Neuropeptide Receptor Neurophysiology - biologic function Organism Outcome Parents Partner in relationship Pattern Personality Disorders Phenotype Physiology Process Psychopathology RNA RNA Interference Research Role Scientist Social Behavior Social Environment Source Structure Students System Temperament Training Underrepresented Minority United States National Institutes of Health V1a vasopressin receptor Variant Vasopressins Violence War Woman Work Youth affiliative behavior behavior influence brain behavior caregiving cohesion design graduate student improved innovation insight interest knock-down male meetings neuromechanism novel offspring prairie vole programs public health relevance pup receptor relating to nervous system research study social social attachment social implication

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research program is to understand the neurobiology of monogamy and the social behaviors that comprise this unique mating system. The proposed studies will examine how causal manipulations of a neuropeptide receptor that regulates social behavior, V1aR, influence the behavioral phenotypes constituting mammalian monogamy. Monogamy is characterized by parental care, social affiliation, and territorial aggression. Unfortunately, most studies investigating specific mechanisms underlying monogamy typically focus on these behaviors in isolation. Furthermore, several studies have revealed that each of these behaviors is affected by the action of arginine vasopressin on V1a receptors in a neural structure known as the lateral septum (LS). Because of these common influences, the components of monogamous behavior are probably mechanistically intertwined and best studied in concert. The PI hypothesizes that targeted manipulation of V1aR in the LS will coordinate diverse attributes of temperament related to attachment, aggression and care-giving. The PI utilizes the monogamous prairie vole because much of what has been learned about the neurobiology of attachment has been gained from work with this model species. There are two objectives. Objective 1 will identify the causal role of lateral septum V1aR on monogamous behavior using interfering RNA (RNAi) to silence V1aR gene expression. The innovation of using RNAi for behavioral studies is novel. The PI will artificially eliminate V1aR expression to investigate its role in distinct but related social domains to provide a deeper understanding of the contribution of septal V1aR to 'monogamy'. Objective 2 aims to understand the impact of dysfunctional paternal care on offspring development and social behavior. To this end, the PI will knockdown septal V1aR in fathers and measure how such manipulations affect the physical and behavioral development of their offspring as pups and juveniles. The combination of these studies will provide a clearer picture of the behavioral and developmental consequences of septal function, an area of much interest but little cohesion. This proposal significantly advances the NIH mission to pursue fundamental knowledge about the behavior of living systems and is designed to improve both mental health and health in the process of human development. An implicit third aim of this proposal is to cultivate and retain young scientists, particularly women and underrepresented minorities. This project will support two undergraduate and two graduate students, one of whom is African American, three of whom are women, and all of whom have immense potential. Funding this project will, therefore, train exceptional students interested in understanding the neural mechanisms that subserve social attachment, aggression, parental care, and offspring development, and prepare them for professions in biomedical and behavioral research. This work will reveal much of the neurobiology that underlies fundamental behaviors constituting mammalian monogamy, and could foster a deeper understanding of mechanisms regulating human social behavior and its dysfunction. PUBLIC HEALTH RELEVANCE: By exploring the substrates of socio-emotional behavior and temperament, this work should provide insight into the biological sources of care-giving, and familial violence. These studies could contribute toward progress in understanding and ultimately treating human disorders characterized by deficits in social attachment (such as autism) and those associated with excessive aggression (such as domestic violence, conduct disorder, or psychopathology). Study of the social environment of developing offspring will provide insight into the importance of paternal care on child health and development and its ultimate importance in offspring behavior as adults.

描述（由申请人提供）：本研究项目的长期目标是了解一夫一妻制的神经生物学和构成这种独特交配系统的社会行为。拟议的研究将研究调节社会行为的神经肽受体V1aR的因果操纵如何影响构成哺乳动物一夫一妻制的行为表型。一夫一妻制的特点是亲代照顾、社会关系和领土侵略。不幸的是，大多数调查一夫一妻制背后具体机制的研究通常都是孤立地关注这些行为。此外，一些研究表明，这些行为中的每一种都受到精氨酸抗利尿素对神经结构中称为侧隔（LS）的V1a受体的作用的影响。由于这些共同的影响，一夫一妻制行为的组成部分可能是机械地交织在一起的，最好是一起研究。PI假设有针对性地操纵LS中的V1aR将协调与依恋、攻击和照顾相关的气质的多种属性。PI之所以使用一夫一妻制的草原田鼠，是因为已经从这个模式物种的工作中获得了很多关于依恋的神经生物学知识。有两个目标。目的1将通过干扰RNA （RNAi）沉默V1aR基因表达来确定侧隔膜V1aR对一夫一妻制行为的因果作用。使用RNAi进行行为研究的创新是新颖的。PI将人为地消除V1aR表达，以研究其在不同但相关的社会领域中的作用，从而更深入地了解间隔V1aR对“一夫一妻制”的贡献。目的2旨在了解不正常的父权照顾对后代发育和社会行为的影响。为此，PI将破坏父亲的间隔V1aR，并测量这种操作如何影响其后代在幼年和幼年时期的身体和行为发育。这些研究的结合将为室间隔功能的行为和发育后果提供更清晰的画面，这是一个非常有趣但缺乏凝聚力的领域。该提案显著推进了NIH追求生命系统行为基础知识的使命，旨在改善人类发展过程中的心理健康和健康。这项提议隐含的第三个目标是培养和留住年轻科学家，尤其是女性和未被充分代表的少数族裔。这个项目将资助两名本科生和两名研究生，其中一名是非裔美国人，三名女性，她们都有巨大的潜力。因此，资助这个项目将培养对理解支持社会依恋、攻击、父母照顾和后代发展的神经机制感兴趣的优秀学生，并为他们从事生物医学和行为研究做好准备。这项工作将揭示构成哺乳动物一夫一妻制基本行为的许多神经生物学基础，并可能促进对调节人类社会行为及其功能障碍的机制的更深入理解。