Understanding the neural basis of social attachment

项目总结 社会依恋构成了社会组织各个层面上人际关系的基础，从 父母和孩子之间的关系，恋人之间的关系，与同龄人和团体的关系。中途中断 依恋发生在各种精神疾病中，严重的神经精神障碍常常表现出来。 伴随着社会依恋和认知的戏剧性崩溃。尽管社交依恋起着至关重要的作用，但几乎没有 关于依恋背后的神经和遗传机制是已知的。小鼠和其他遗传模型 生物体不会表现出持久的社会依恋，这排除了对这些行为的遗传分析。 草原田鼠是一种小型啮齿动物，在配偶之间表现出社会一夫一妻制或结对纽带。配对键合 形成导致了许多其他与生俱来的社会行为的戏剧性变化。因此，草原田鼠从事一种 丰富的社会行为令人惊叹地反映了人类的依恋。开创性的工作确定了 多肽激素加压素(AVP)和催产素(OXT)，作为田鼠和动物配对结合的关键介质 人类的社会认知和行为。这些发现表明，社会的遗传和神经控制 依恋可能是保守的，而且确实激发了临床试验，试图使用这些激素来 改善由于神经精神疾病造成的社会认知障碍。然而，这些是如何 控制复杂社会行为的特定方面的途径和其他基因仍不清楚。 到目前为止，我们还不能理解OXTR和V1aR是如何控制模式的 对伴侣或陌生人做出反应的神经活动。我们已经产生了携带OXTR突变的草原田鼠 和V1aR，完全消除了这些受体的功能，并开发了光学 草原自由活动动物行为过程中神经活动的记录和基因表达谱 田鼠。使用这个强大的系统，我们现在可以测试OXTR和V1aR控制不同方面的假设 1)配对结合和成人社交依恋行为，2)伴侣或陌生人特有的神经模式 在社会互动过程中田鼠大脑特定区域的活动，以及3)基因表达的变化 这些神经群体中潜在的社会依恋。我们的初步工作表明，OXTR信号是 草原田鼠的配对不需要遗传上的结合，因此，对 社交依恋背后的神经和分子通路可能为我们提供新的见解 调节这种长期的社会记忆和联系的形成。这些研究将阐明 OXTR和V1aR促进依恋并最终提供新的治疗方法的机制 各种精神疾病的治疗方法。

PROJECT SUMMARY Social attachments form the basis of human relationships at every level of social organization, from relationships between parents and children, romantic partners, to peers and group affiliation. Disruptions in attachment occur across the spectrum of mental illness, and severe neuropsychiatric disorders often manifest with a dramatic collapse of social attachment and cognition. Despite this critical role of social attachment, little is known regarding the neural and genetic mechanisms underlying attachment. Mice and other genetic model organisms do not exhibit enduring social attachments, precluding genetic analysis of these behaviors. Prairie voles are small rodents that display social monogamy, or pair bonds, between mates. Pair bond formation results in dramatic changes to many other innate social behaviors. Thus, prairie voles engage in a rich repertoire of social behaviors that strikingly mirror attachment in humans. Pioneering work identified the peptide hormones vasopressin (Avp) and oxytocin (Oxt), as critical mediators of pair bonding in voles and social cognition and behaviors in humans. These findings suggest that the genetics and neural control of social attachment may be conserved, and indeed, have inspired clinical trials seeking to use these hormones to ameliorate disruptions in social cognition due to neuropsychiatric conditions. Nevertheless, how these pathways and other genes function to control specific aspects of complex social behaviors remains unknown. Until now, we have been unable to understand how OxtR and V1aR function to control patterns of neural activity in response to partners or strangers. We have generated prairie voles bearing mutations in OxtR and V1aR that completely eliminate the function of these receptors, and developed approaches for optical recording of neural activity in freely moving animals during behavior and profiling of gene expression in prairie voles. Using this powerful system, we can now test the hypothesis that OxtR and V1aR control distinct aspects of 1) pair bonding and adult social attachment behaviors, 2) partner- or stranger-specific patterns of neural activity in specific regions of the vole brain during social interactions, and 3) changes in gene expression underlying social attachment in these neural populations. Our preliminary work suggests that OxtR signaling is not required genetically for pair bonding in prairie voles, and, thus, that a more refined understanding of the neural and molecular pathways underlying social attachment may provide new insights into the pathways that mediate the formation of such long term social memory and affiliation. These studies will elucidate the mechanisms by which OxtR and V1aR facilitate attachment and, eventually, inform new therapeutic approaches across the spectrum of mental illness.