Paternal Care, Affiliation and Vasopressin: Mechanisms of Monogamy

描述(由申请者提供)：该研究计划的长期目标是了解一夫一妻制的神经生物学和组成这一独特交配系统的社会行为。这项拟议的研究将研究调节社会行为的神经肽受体V1aR的因果操作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父母关爱、社会联系和领土侵略。不幸的是，大多数研究一夫一妻制背后的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，这些行为都受到精氨酸加压素对外侧隔(LS)神经结构中V1a受体作用的影响。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相互交织在一起的，最好是协调一致地研究。PI假设，在LS中有针对性地操纵V1aR将协调与依恋、攻击性和照顾有关的气质的不同属性。PI利用了一夫一妻制的草原田鼠，因为许多关于依恋的神经生物学的知识都是从与这种模式物种的工作中获得的。有两个目标。目的1利用干扰RNA(RNAi)沉默V1aR基因的表达，以确定外侧隔V1aR在一夫一妻制行为中的作用。利用RNAi进行行为研究的创新之处是新颖的。PI将人工消除V1aR的表达，以调查其在不同但相关的社会领域中的作用，以提供对隔区V1aR对一夫一妻制的贡献的更深层次的理解。目的了解功能失调的父系照料对子代发育和社会行为的影响。为此，PI将敲除父亲的隔区V1aR，并测量这种操作如何影响其幼崽和青少年后代的身体和行为发育。这些研究的结合将为隔膜功能的行为和发育后果提供更清晰的图景，隔膜功能是一个很有兴趣但很少凝聚力的领域。这项建议大大推进了美国国立卫生研究院追求生命系统行为基本知识的使命，旨在改善心理健康和人类发展过程中的健康。这项提议的第三个隐含目标是培养和留住年轻科学家，特别是女性和代表性不足的少数群体。该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，三名是女性，他们都有巨大的潜力。因此，资助这个项目将培养对了解有助于社会依恋、攻击性、父母照顾和后代发展的神经机制感兴趣的优秀学生，并为他们在生物医学和行为研究领域的职业做好准备。这项工作将揭示构成哺乳动物一夫一妻制的基本行为的大部分神经生物学，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层次理解。 公共卫生相关性：通过探索社会情绪行为和气质的基础，这项工作应该提供对照顾和家庭暴力的生物来源的洞察。这些研究有助于在理解和最终治疗以社会依恋缺陷为特征的人类疾病(如自闭症)和与过度攻击性有关的疾病(如家庭暴力、行为障碍或精神病理学)方面取得进展。对发育中的后代的社会环境的研究将有助于深入了解父亲的照顾对儿童健康和发育的重要性，以及它在成年后的后代行为中的最终重要性。

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.