Dissecting the neural control of social attachment

剖析社会依恋的神经控制

• 批准号: 8536385
• 负责人: Nirao Mahesh Shah
• 金额: $ 74.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536385
• 关键词: Anatomy; Anxiety; Autistic Disorder; Behavior; Behavioral; Brain; Employee Strikes; Gene Targeting; Genetic; Healed; Human; Individual; Knock-in Mouse; Knock-out; Lead; Maps; Marriage; Mediating; Mental disorders; Microtus; Molecular; Mus; Neuropeptides; Oxytocin; Partner in relationship; Pathway interactions; Play; Resolution; Rodent; Role; Rupture; Shapes; Signal Transduction; Stress; Systems Analysis; Vasopressins; Zebrafish; effective therapy; embryonic stem cell; healing; in vivo; insight; interest; neural circuit; neuroregulation; positional cloning; relating to nervous system; research study; social; social attachment; tool

We are interested in understanding how the brain generates social attachments. Humans form enduring social relationships that shape the rules for interacting with other individuals. Ruptured social ties are often the first sign of mental illness, and are usually the most difficult to heal. Even in healthy individuals, breakdown of a social relationship such as marriage leads to a dramatic increase in stress and anxiety. In humans, the neuropeptides vasopressin and oxytocin play critical roles in the formation of social attachments. Moreover, altered signaling of these neuropeptide pathways is associated with a decline in the quality of social relationships and with serious illnesses such as autism. Mice, zebrafish, worms and fruitflies do not display social attachments, precluding the use of genetic tools to dissect the neural and molecular networks that mediate these behaviors. Voles, which are small rodents, display striking social bonds such that a mated pair displays enduring co-habitation and sexual fidelity. As in humans, vasopressin and oxytocin are critical for the formation of social ties in voles. Progress in dissecting the neural circuits that mediate social attachment is stymied due to the lack of gene targeting approaches in voles. We propose to develop the reverse genetic strategies in voles that have revolutionized experimental manipulations in the mouse. We propose to develop embryonic stem cells to enable targeted gene knock-out and knock-in experiments in vivo. We will combine these genetic tools with behavioral analysis, high resolution anatomic and functional neural circuit mapping, and systems analysis of signaling to understand how the brain normally generates social attachments. These insights will be applied to understanding how neural circuits malfunction in autism and other mental disorders. Our studies should eventually lead to effective therapies to restore the ability to form enduring social attachments.

我们有兴趣了解大脑如何产生社交依恋。人类形态 持久的社会关系塑造了与其他人互动的规则。破裂 社会关系往往是精神疾病的第一个迹象，而且通常是最难治愈的。 即使对于健康的人来说，婚姻等社会关系的破裂也会导致 压力和焦虑急剧增加。在人类中，神经肽加压素和 催产素在社会依恋的形成中起着至关重要的作用。此外，改变的信号 这些神经肽途径与社会关系质量下降有关 以及患有自闭症等严重疾病。小鼠、斑马鱼、蠕虫和果蝇不显示 社会依恋，妨碍使用遗传工具来剖析神经和分子 调解这些行为的网络。田鼠是一种小型啮齿动物，具有惊人的社交能力 使伴侣表现出持久的同居和性忠诚的纽带。就像人类一样， 加压素和催产素对于田鼠社会关系的形成至关重要。进展情况 由于缺乏基因，解剖介导社会依恋的神经回路受到阻碍 田鼠的靶向方法。我们建议在田鼠中开发反向遗传策略 这彻底改变了小鼠的实验操作。我们建议开发 胚胎干细胞能够在体内进行靶向基因敲除和敲入实验。我们 将把这些遗传工具与行为分析、高分辨率解剖学和 功能神经回路映射和信号系统分析，以了解大脑如何 通常会产生社交依恋。这些见解将用于理解如何 自闭症和其他精神障碍中的神经回路故障。我们的研究最终应该 导致有效的治疗以恢复形成持久社会依恋的能力。