Understanding the neural basis of social attachment

了解社会依恋的神经基础

• 批准号: 10599715
• 负责人: Devanand Sadanand Manoli
• 金额: $ 9.03万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599715
• 关键词: 3-Dimensional; Adult; Agonistic Behavior; Amygdaloid structure; Animal Model; Animals; Behavior; Behavioral; Behavioral Assay; Biological Assay; Cells; Clinical Trials; Complex; Continuing Education; Data; Detection; Female; Gene Expression; Generations; Genetic; Hormone use; Human; Lateral; Manuals; Medial; Mediating; Mediator of activation protein; Medical; Medicine; Mental disorders; Microtus; Mutation; Neurons; Neurosciences; Nucleus Accumbens; Optics; Other Genetics; Oxytocin; Oxytocin Receptor; Pair Bond; Partner in relationship; Pathway interactions; Pattern; Phase; Play; Population; Posture; Process; Rodent; Role; Signal Transduction; Social Behavior; Social Interaction; Stimulus; Testing; Time; Training; Vasopressins; Viral; Work; affiliative behavior; behavior influence; career; computer science; design; experience; gene function; genetic analysis; improved; insight; loss of function mutation; male; mouse genetics; neural patterning; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; novel therapeutic intervention; parent grant; peptide hormone; prairie vole; preference; receptor; receptor function; relating to nervous system; response; sex; social; social attachment; social cognition; social organization

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.

项目概要 该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，以便她能够最好地将她的计算机科学背景与她的预期职业生涯相结合 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。依恋的破坏发生在各种精神疾病和严重的神经精神疾病中 疾病通常表现为社会依恋和认知的急剧崩溃。尽管发挥了这一关键作用 社会依恋，关于依恋背后的神经和遗传机制知之甚少。小鼠和 其他遗传模型生物不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。 草原田鼠是小型啮齿动物，在配偶之间表现出社会一夫一妻制或配对关系。配对债券 形成会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 一系列社会行为惊人地反映了人类的依恋。开创性工作确定了肽 激素加压素 (Avp) 和催产素 (Oxt)，作为田鼠配对和社会认知的关键介质 以及人类的行为。这些发现表明，社会依恋的遗传学和神经控制可能 被保存下来，并且确实激发了寻求使用这些激素来改善干扰的临床试验 由于神经精神疾病导致的社会认知能力下降。然而，这些途径和其他基因如何 控制复杂社会行为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 如何发挥作用来控制神经模式 对伙伴或陌生人做出反应的活动。我们已经培育出携带 OxtR 突变的草原田鼠 V1aR 完全消除了这些受体的功能，并且令人惊讶的是，OxtR 不是 是配对关系所必需的，但有利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进行更精细的理解可能会 为调解归属感的途径提供新的见解。本补充旨在提供培训 为实验神经科学领域的申请人提供便利，以促进她的继续教育，为她的预期做好准备 研究生和医学生涯。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结对结合的行为模块，并确定如何 特定 OxtR 神经元群的激活会影响这些行为。这些研究将阐明 OxtR 和 V1aR 促进附着并最终为新的治疗方法提供信息的机制 涵盖各种精神疾病。