Understanding the neural basis of social attachment

了解社会依恋的神经基础

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要该补充旨在为申请人提供实验的经验和培训神经科学，以便她最好将自己的计算机科学背景与她的意图职业整合在一起神经科学和医学。社会依恋构成了社会各个层面的人际关系的基础组织。依恋的干扰发生在精神疾病的范围内，以及严重的神经精神病学疾病通常表现为社会依恋和认知的巨大崩溃。尽管至关重要社会依恋，关于依恋的神经和遗传机制知之甚少。老鼠和其他遗传模型生物没有表现出持久的社会依恋，排除了这些遗传分析行为。草原田鼠是伴侣之间表现出社交一夫一妻制或成对纽带的小啮齿动物。配对键形成导致许多其他先天社会行为发生巨大变化。因此，草原田鼠从事富人社会行为的曲目恰好反映了人类中的依恋。开创性工作确定了肽激素加压素（AVP）和催产素（OXT），作为田鼠和社会认知的伴侣键合的关键介体和人类的行为。这些发现表明，社会依恋的遗传学和神经控制可能保持保存，并且确实启发了寻求使用这些激素改善干扰的临床试验由于神经精神疾病而引起的社会认知。然而，这些途径和其他基因如何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，我们一直无法理解OXTR和V1AR如何控制神经模式响应伴侣或陌生人的活动。我们已经在Oxttr中产生了带有突变的草原田鼠， V1AR完全消除了这些受体的功能，并明显地确定了OXTR不是配对键所需的要求，但促进伴侣的偏好和性别特定于性别控制亲社会行为陌生人。因此，对社会依恋为基础的行为过程的更精致的理解可能提供有关介导隶属关系的途径的新见解。该补充旨在提供培训对于实验性神经科学领域的申请人，以促进她的继续教育研究生和医疗职业。在这里，我们建议优化和实施公正的自动行为跟踪和检测以了解促进配对键合的行为模块，并确定如何 OXTR神经元特定种群的激活会影响这些行为。这些研究将阐明 OXTR和V1AR促进附着并最终告知新的治疗方法的机制跨精神疾病。