Dissecting the neural control of social attachment

描述 摘要 我们感兴趣的是了解大脑是如何产生社交依恋的。人类形成了持久的社会关系，这些社会关系塑造了与其他人互动的规则。社会关系破裂通常是精神疾病的第一个迹象，通常也是最难愈合的。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的急剧增加。在人类中，神经肽加压素和催产素在社交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、蠕虫和果蝇不会表现出社交依恋，这排除了使用遗传工具来剖析调节这些行为的神经和分子网络的可能性。田鼠是一种小型啮齿动物，表现出惊人的社会纽带，以至于交配的一对表现出持久的同居和对性的忠诚。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。由于缺乏对田鼠基因打靶的方法，在解剖调节社会依恋的神经回路方面的进展受到阻碍。我们建议在田鼠身上开发反向遗传策略，这些策略已经彻底改变了小鼠的实验操作。我们建议开发胚胎干细胞，以便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、高分辨率解剖和功能神经回路图谱以及信号系统分析结合起来，以了解大脑正常情况下如何产生社交依恋。这些见解将被用来理解自闭症和其他精神障碍的神经回路是如何运作的。我们的研究最终应该会带来有效的治疗方法，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