Molecular and Neural Networks Underlying Social Attachment

社会依恋背后的分子和神经网络

• 批准号: 9370484
• 负责人: Karen L. Bales
• 金额: $ 63.76万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-21 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9370484
• 关键词: AVPR1A gene; Adult; Applications Grants; Autistic Disorder; Behavior; Behavioral; Behavioral Genetics; Binding; Biological Models; Biological Neural Networks; Caring; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Development; Diagnostic; Drug Kinetics; Emotional; Empathy; Employee Strikes; Exhibits; Failure; Family member; Fishes; Friends; Gene Expression; Gene Targeting; Generations; Genes; Genetic; Genetic Models; Glues; Health; Human; In Situ Hybridization; Knock-out; Maintenance; Mammalian Genetics; Mammals; Mental Depression; Mental Health; Mental disorders; Microtus; Modeling; Molecular; Molecular Genetics; Mus; Neural Pathways; Neurobiology; Neurons; Neuropeptides; Oxytocin; Pair Bond; Partner in relationship; Pathway interactions; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Pharmacology Study; Play; Property; Publishing; Reagent; Regulation; Ribosomes; Rodent; Role; Rupture; Schizophrenia; Signal Pathway; Signal Transduction; Social Behavior; Social Controls; Social Interaction; Specific qualifier value; Specificity; Spouses; System; Techniques; Technology; Testing; Therapeutic Intervention; Time; Transcript; Trust; Vasopressin Receptor; Vasopressins; affiliative behavior; autism spectrum disorder; behavioral study; experimental study; fly; genetic approach; genetic manipulation; healing; induced pluripotent stem cell; innovation; insight; member; mutant; neural circuit; neurobiological mechanism; neuromechanism; neuropsychiatry; next generation; novel; prairie vole; public health relevance; pup; receptor; receptor binding; severe mental illness; sex; social; social attachment; success; tool

 DESCRIPTION (provided by applicant): This grant application seeks to uncover the molecular and neural networks underlying social attachment behaviors in prairie voles. Humans form attachments at many levels of social interactions, including with spouses, family members, friends, and other members of the community. The neurobiological mechanisms that control the formation and maintenance of social attachment remain poorly understood. This is in part because traditional genetic model systems such as mice, fish, flies, and worms do not exhibit social attachment behavior as adults, precluding the use of powerful molecular genetic approaches to dissect mechanisms underlying social attachment behavior. Prairie voles are small rodents that form an enduring social bond between adults, and they also display other related afflictive behaviors. Pharmacologic studies in prairie voles have implicated vasopressin and oxytocin signaling in the control of social attachment behaviors. However, there are significant limitations of these pharmacological manipulations such that the genetic requirement of specific neuropeptide signaling pathways remains unclear. Progress in uncovering the molecular and neural circuit basis of social attachments in prairie voles has been slowed by the absence of gene targeting techniques as well as by the absence of identification of behaviorally-salient neurons. In this grant application, we propose to develop gene targeting technology in prairie voles, focusing on vasopressin and oxytocin signaling pathways (Aim 1). In Aim 2, we propose to analyze behavioral deficits in social attachment in prairie voles genetically mutant for these signaling pathways. Finally, in Aim 3 we propose developing molecular tools to uncover genetic and neural pathways underlying social attachment in prairie voles. Taken together, our studies will enable gene targeting in prairie voles and elucidate neural mechanisms that control social attachment behavior. Health relatedness: Social attachments are thought to be critical for our mental health and for success in personal and professional interactions. Failure to form or maintain social attachments is often an early indicator of a serious mental illness such as autism spectrum disorder or schizophrenia. Strikingly, vasopressin and oxytocin are also thought to play a critical role in human social attachments, and dysregulated signaling via these neuropeptide pathways has been implicated in autism spectrum disorders. Our proposal seeks to establish the prairie vole as a new mammalian genetic model system and to uncover mechanisms underlying social attachment behavior. These advances may therefore provide a useful model system to study social behaviors relevant to human health and mental illnesses.

 描述（由申请人提供）：这项资助申请旨在揭示草原田鼠社会依恋行为背后的分子和神经网络。人类在社会互动的许多层面上形成依恋，包括与配偶，家庭成员，朋友和社区的其他成员。控制社会依恋形成和维持的神经生物学机制仍然知之甚少。这部分是因为传统的遗传模型系统，如小鼠，鱼，苍蝇和蠕虫不表现出社会依恋行为作为成年人，排除了使用强大的分子遗传学方法来剖析社会依恋行为的机制。草原田鼠是一种小型啮齿动物，在成年人之间形成了持久的社会纽带，它们也表现出其他相关的痛苦行为。对草原田鼠的药理学研究表明，加压素和催产素信号在社会依恋行为的控制中起作用。然而，这些药理学操作存在显著的局限性，使得特定神经肽信号传导途径的遗传要求仍然不清楚。由于缺乏基因靶向技术以及缺乏对行为突出神经元的识别，揭示草原田鼠社会依恋的分子和神经回路基础的进展已经放缓。在这项拨款申请中，我们建议在草原田鼠中开发基因靶向技术，重点是加压素和催产素信号通路（Aim 1）。在目标2中，我们提出分析遗传突变的草原田鼠在社会依恋方面的行为缺陷， 这些信号通路。最后，在目标3中，我们提出开发分子工具来揭示草原田鼠社会依恋的遗传和神经通路。总之，我们的研究将使草原田鼠的基因靶向和阐明控制社会依恋行为的神经机制。健康相关性：社会依恋被认为对我们的心理健康以及个人和专业互动的成功至关重要。不能形成或维持社会依恋通常是严重精神疾病的早期指标，如自闭症谱系障碍或精神分裂症。引人注目的是，加压素和催产素也被认为在人类社会依恋中起着关键作用，通过这些神经肽途径的失调信号与自闭症谱系障碍有关。我们的建议旨在建立草原田鼠作为一个新的哺乳动物遗传模型系统，并揭示社会依恋行为的机制。因此，这些进展可能为研究与人类健康和精神疾病相关的社会行为提供一个有用的模型系统。