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会依恋。人类形成 持久的社会关系，以塑造与其他人互动的规则。破裂 社交关系通常是精神疾病的第一个迹象，通常是最难治愈的迹象。 即使在健康的个体中，婚姻等社会关系的细分也会导致 压力和焦虑的急剧增加。在人类中，神经肽加压素和 催产素在社会依恋的形成中起关键作用。此外，改变的信号传导 这些神经肽途径与社会关系质量的下降有关 并患有自闭症等严重疾病。老鼠，斑马鱼，蠕虫和水果粉不显示 社会依恋，排除使用遗传工具来剖析神经和分子 介导这些行为的网络。田鼠是小啮齿动物，展示了惊人的社交 债券使一对配对表现出持久的共同限制和性保真度。就像在人类中一样 加压素和催产素对于田鼠的社会关系形成至关重要。进步 由于缺乏基因而剖析介导社会依恋的神经回路受到阻碍 田鼠的靶向方法。我们建议在田鼠中发展反向遗传策略 彻底改变了小鼠中的实验操作。我们建议发展 胚胎干细胞能够在体内实现靶向基因敲除和敲除实验。我们 将将这些遗传工具与行为分析，高分辨率解剖和 功能性神经电路映射和信号的系统分析，以了解大脑如何 通常会产生社会依恋。这些见解将用于了解如何 自闭症和其他精神障碍中的神经电路故障。我们的研究最终应该 导致有效的疗法恢复形成持久社会依恋的能力。