Dissecting the neural control of social attachment

描述 摘要 我们有兴趣了解大脑如何产生社会依恋。人类形成了持久的社会关系，这些关系塑造了与其他个体互动的规则。社会关系破裂往往是精神疾病的第一个征兆，而且通常是最难治愈的。即使在健康的个体中，婚姻等社会关系的破裂也会导致压力和焦虑的急剧增加。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，这些神经肽通路的信号改变与社会关系质量的下降和自闭症等严重疾病有关。老鼠、斑马鱼、蠕虫和果蝇不显示社会依恋，排除了使用遗传工具来解剖介导这些行为的神经和分子网络。田鼠是一种小型啮齿动物，它们表现出惊人的社会关系，以至于一对配偶表现出持久的同居和性忠诚。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。由于缺乏田鼠的基因靶向方法，在解剖介导社会依恋的神经回路方面的进展受到阻碍。我们建议在田鼠中开发反向遗传策略，从而彻底改变小鼠的实验操作。我们建议开发胚胎干细胞，使有针对性的基因敲除和敲入体内实验。我们将联合收割机与行为分析，高分辨率解剖和功能神经回路映射，以及信号的系统分析结合起来，以了解大脑通常如何产生社会依恋。这些见解将被应用于理解自闭症和其他精神疾病的神经回路如何发生故障。我们的研究最终应该会导致有效的治疗方法，以恢复形成持久的社会依恋的能力。 公共卫生相关性 SoC

DESCRIPTION Abstract 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. Public Health Relevance Soc