Dissecting the neural control of social attachment

剖析社会依恋的神经控制

• 批准号: 8296585
• 负责人: Nirao Mahesh Shah
• 金额: $ 76.48万
• 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/8296585
• 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 持久的社会关系塑造了与其他个体互动的规则。破裂 社会关系往往是精神疾病的第一个征兆，而且通常是最难治愈的。 即使是健康的人，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，神经肽血管加压素和 催产素在社会依恋的形成中起着关键作用。此外， 这些神经肽通路与社会关系质量的下降有关 以及患有严重疾病如自闭症的患者。老鼠、斑马鱼、蠕虫和果蝇不会 社会依恋，排除了使用遗传工具来解剖神经和分子 网络来调节这些行为。田鼠是小型啮齿动物， 一对伴侣表现出持久的同居和性忠诚的纽带。和人类一样， 后叶加压素和催产素对田鼠社会关系的形成至关重要。进展 由于缺乏基因，解剖调节社会依恋的神经回路受到阻碍， 在田鼠中的定位方法。我们建议在田鼠中发展反向遗传策略 彻底改变了老鼠的实验操作。我们建议发展 胚胎干细胞，使靶基因敲除和敲入实验在体内。我们 将联合收割机这些遗传工具与行为分析，高分辨率解剖和 功能神经回路映射和信号系统分析，以了解大脑如何 通常会产生社会依恋。这些见解将被应用于理解如何 自闭症和其他精神疾病的神经回路故障。我们的研究最终应该 导致有效的治疗，以恢复形成持久的社会依恋的能力。