Paternal Care, Affiliation and Vasopressin: Mechanisms of Monogamy

描述（由申请人提供）：本研究计划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。拟议的研究将探讨如何因果操纵的神经肽受体，调节社会行为，V1aR，影响行为表型构成哺乳动物一夫一妻制。一夫一妻制的特点是父母照顾、社会关系和领土侵略。不幸的是，大多数研究一夫一妻制的具体机制通常集中在孤立的这些行为。此外，一些研究表明，这些行为中的每一个都受到精氨酸加压素对称为外侧隔（LS）的神经结构中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，最好在音乐会上进行研究。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不同属性。PI使用一夫一妻制的草原田鼠，因为我们已经从这个模型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利用RNA干扰技术沉默V1aR基因的表达，以确定侧隔V1aR在一夫一妻制行为中的作用。使用RNAi进行行为研究的创新是新颖的。PI将人工消除V1aR表达，以研究其在不同但相关的社会领域中的作用，从而更深入地了解隔V1aR对“一夫一妻制”的贡献。目的2旨在了解父亲照顾功能失调对后代发育和社会行为的影响。为此，PI将敲除父亲的隔V1aR，并测量这种操作如何影响其后代作为幼崽和青少年的身体和行为发育。这些研究的结合将提供一个更清晰的画面的行为和发展的后果隔功能，一个领域的兴趣，但很少凝聚力。该提案大大推进了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。这一建议的第三个隐含目的是培养和留住年轻科学家，特别是妇女和代表性不足的少数民族。该项目将支持两名本科生和两名研究生，其中一名是非洲裔美国人，三名是女性，他们都有巨大的潜力。因此，资助这个项目将培养有兴趣了解有助于社会依恋，侵略，父母照顾和后代发展的神经机制的优秀学生，并为他们在生物医学和行为研究方面的职业做好准备。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。 公共卫生相关性：通过探索社会情感行为和气质的基底，这项工作应该提供对护理和家庭暴力的生物来源的洞察。这些研究可能有助于理解并最终治疗以社会依恋缺陷为特征的人类疾病（如自闭症）以及与过度攻击相关的疾病（如家庭暴力，行为障碍或精神病理学）。研究发育中的后代的社会环境将提供洞察力的重要性，父亲的照顾对儿童的健康和发展，其最终的重要性，在后代的行为作为成年人。

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.