Understanding the neural basis of social attachment

项目摘要 本补充材料旨在为申请人提供实验方面的经验和培训 神经科学，使她可以最好地结合她的背景，在计算机科学与她打算的职业生涯， 神经科学和医学。社会依恋构成了社会各个层面的人际关系的基础。 organization.依恋的中断发生在精神疾病的各个方面， 失调常常表现为社会依附和认知的急剧崩溃。尽管这一关键作用， 关于社会依恋，人们对依恋背后的神经和遗传机制知之甚少。小鼠和 其他遗传模式生物没有表现出持久的社会依恋，排除了对这些生物的遗传分析。 行为。 草原田鼠是一种小型啮齿类动物，在配偶之间表现出社会性的一夫一妻制，或称成对关系。对键 形成导致许多其他先天社会行为的巨大变化。因此，草原田鼠从事丰富的 这些社会行为的一系列特征与人类的依恋有着惊人的相似。开创性的工作确定了这种肽 后叶加压素（Avp）和催产素（Oxt）是田鼠配对和社会认知的关键调节因子 和人类的行为。这些发现表明，社会依恋的遗传和神经控制可能 事实上，它已经激发了寻求使用这些激素来改善干扰的临床试验。 在社会认知方面的影响然而，这些途径和其他基因 控制复杂社会行为的特定方面的功能仍然未知。 到目前为止，我们还无法理解OxtR和V1aR是如何控制神经细胞的模式的。 对伴侣或陌生人的反应。我们已经产生了携带OxtR突变的草原田鼠， V1aR完全消除这些受体的功能，并确定，惊人的是，OxtR不是 这是配对所必需的，但有助于伴侣偏好和性别特异性控制亲社会行为， 陌生人因此，对社会依恋背后的行为过程的更精确的理解， 提供了新的见解的途径，介导的联系。本补充材料旨在提供培训 为实验神经科学的申请人，以促进她的继续教育，为她准备她的预期 毕业生和医学生涯。在这里，我们建议优化和实现无偏见的自动化行为 跟踪和检测，以了解促进配对的行为模块，并确定如何 OxtR神经元的特定群体的激活影响这些行为。这些研究将阐明 OxtR和V1aR促进附着的机制，并最终为新的治疗方法提供信息 在精神疾病的范围内。

PROJECT SUMMARY This supplement is designed to provide the applicant with experience and training in experimental neuroscience so that she may best integrate her background in computer science with her intended career in neuroscience and medicine. Social attachments form the basis of human relationships at every level of social organization. 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 determined, strikingly, that OxtR is not required for pair bonding, but facilitates partner preference and sex-specifically controls prosocial behavior with strangers. Thus, a more refined understanding of the behavioral processes underlying social attachment may provide new insights into the pathways that mediate affiliation. This supplement is designed to provide training for the applicant in experimental neuroscience to facilitate her continuing education prepare her for her intended graduate and medical career. Here we propose to optimize and implement unbiased automated behavioral tracking and detection to understand the behavioral modules that facilitate pair bonding, and determine how activation of specific populations of OxtR neurons influences these behaviors. 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.