Understanding the neural basis of social attachment

项目总结 本附录旨在为申请人提供实验方面的经验和培训。 这样她就可以最好地把她在计算机科学方面的背景与她打算在 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 组织。依恋中断发生在各种精神疾病和严重的神经精神疾病 障碍通常表现为社会依恋和认知的戏剧性崩溃。尽管这一关键作用是 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。老鼠和 其他遗传模式生物不会表现出持久的社会依恋，这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，草原田鼠从事着一种富有的 这些社会行为惊人地反映了人类的依恋。开创性的工作鉴定了这种多肽 荷尔蒙加压素(AVP)和催产素(OXT)作为田鼠配对结合和社会认知的关键媒介 以及人类的行为。这些发现表明，社会依恋的遗传和神经控制可能 保守，而且确实启发了寻求使用这些激素来改善干扰的临床试验 由于神经精神疾病造成的社会认知障碍。然而，这些途径和其他基因是如何 控制复杂社会行为的特定方面的功能仍不清楚。 到目前为止，我们还不能理解OXTR和V1aR是如何控制神经模式的 回应伴侣或陌生人的活动。我们已经产生了携带OXTR和OXTR突变的草原田鼠 V1aR，完全消除这些受体的功能，并惊人地确定OXTR不是 对夫妻关系是必需的，但促进了伴侣的偏好和性行为-专门控制亲社会行为 陌生人。因此，对潜在的社会依恋的行为过程的更精细的理解可能 为调解联系的途径提供新的见解。本附录旨在提供培训 对于实验神经科学的申请者，为了促进她的继续教育，她要为她的计划做好准备 毕业和医学生涯。在这里，我们建议优化和实现无偏见的自动行为 跟踪和检测以了解促进配对绑定的行为模块，并确定如何 OXTR神经元特定群体的激活会影响这些行为。这些研究将阐明 OXTR和V1aR促进依恋并最终形成新的治疗方法的机制 所有的精神疾病。

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.