Computational neuroethology in prairie voles: Toward unbiased, systematic detection of social behaviors

草原田鼠的计算神经行为学：对社会行为进行公正、系统的检测

• 批准号: 10382129
• 负责人: Devanand Sadanand Manoli
• 金额: $ 12.2万
• 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/10382129
• 关键词: Adult; Aggressive behavior; Amygdaloid structure; Animal Model; Animals; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; CRISPR/Cas technology; Child; Child Rearing; Clinical Trials; Comparative Study; Complex; Detection; Fiber; Gene Expression; Gene Expression Profiling; Genetic; Group Affiliation; Hormone use; Human; Lateral; Medial; Mediating; Mediator of activation protein; Memory; Mental disorders; Microtus; Molecular; Molecular Profiling; Mutation; Neurons; Nucleus Accumbens; Optics; Other Genetics; Oxytocin; Oxytocin Receptor; Pair Bond; Parents; Partner in relationship; Pathway interactions; Pattern; Peer Group; Photometry; Population; Rodent; Role; Siblings; Signal Transduction; Social Behavior; Social Controls; Social Interaction; System; Territoriality; Testing; Transcript; Vasopressins; Work; gene function; genetic analysis; in vivo; insight; mouse genetics; mutant; neural patterning; neuroethology; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; novel therapeutic intervention; object recognition; parent grant; peptide hormone; prairie vole; preference; receptor; receptor function; relating to nervous system; response; sex; social; social attachment; social cognition; social organization; species difference; transcriptome sequencing

PROJECT SUMMARY- (Parent Grant- No Change) 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.

项目概要-（家长资助-不变） 社会依恋构成了社会组织各个层面的人际关系的基础， 父母和孩子之间的关系，浪漫的合作伙伴，同龄人和团体归属。中断 依恋发生在精神疾病的各个方面，严重的神经精神障碍往往表现为 社会依附和认知的急剧崩溃。尽管社会依恋发挥着关键作用，但很少有 关于依恋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，这就排除了对这些行为进行遗传分析的可能性。 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 丰富的社会行为，这些行为明显反映了人类的依恋。开拓性的工作确定了 肽类激素血管加压素（Avp）和催产素（Oxt），作为田鼠配对的关键介质， 人类的社会认知和行为这些发现表明，遗传学和神经控制的社会 依恋可能是保守的，事实上，已经激发了临床试验，寻求使用这些激素， 改善由于神经精神疾病引起的社会认知中断。然而，这些 控制复杂社会行为的特定方面的途径和其他基因功能仍然未知。 到目前为止，我们还无法理解OxtR和V1 aR是如何发挥作用来控制 神经活动对伴侣或陌生人的反应。我们已经培育出了携带OxtR突变的草原田鼠， 和V1 aR，完全消除这些受体的功能，并开发了光学 记录自由移动动物行为过程中的神经活动和草原基因表达谱 田鼠使用这个强大的系统，我们现在可以测试OxtR和V1 aR控制不同方面的假设 1）配对联结和成人社会依恋行为，2）伴侣或陌生人特定的神经模式， 在社会交往过程中，田鼠大脑特定区域的活动，以及3）基因表达的变化 潜在的社会依恋。我们的初步工作表明，OxtR信号是 在草原田鼠的配对中，基因上并不需要，因此， 作为社会依恋基础的神经和分子通路可能会为研究这些通路提供新的视角， 调解这种长期社会记忆和联系的形成。这些研究将阐明 OxtR和V1 aR促进附着的机制，并最终为新的治疗方法提供信息。 在精神疾病的各个领域都有广泛的应用。