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：
10249294
负责人：
Devanand Sadanand Manoli
金额：
$ 58.59万
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/10249294
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 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 neuropsychiatric disorder neuropsychiatry neuroregulation novel novel therapeutic intervention object recognition 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

项目摘要

PROJECT SUMMARY 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.

项目摘要社会依恋构成了社会组织各个级别的人际关系的基础父母与孩子之间的关系，浪漫的伴侣与同龄人和团体隶属关系。中断依恋在精神疾病的范围内发生，严重的神经精神疾病经常表现出来随着社会依恋和认知的巨大崩溃。尽管社会依恋的关键作用，但很少关于附着的神经和遗传机制已知。小鼠和其他遗传模型生物不会表现出持久的社会依恋，排除对这些行为的遗传分析。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，草原田鼠从事富有的社会行为曲目，它们在人类中的依恋很大程度上反映了依恋。开创性工作确定了肽激素加压素（AVP）和催产素（OXT），作为田鼠配对键的关键介体和人类的社会认知和行为。这些发现表明，社会的遗传和神经控制依恋可能是保守的，实际上已经启发了寻求使用这些激素的临床试验由于神经精神疾病的疾病，可以改善社会认知的干扰。然而，如何这些途径和其他基因来控制复杂社会行为的特定方面，仍然未知。到目前为止，我们一直无法理解OXTR和V1AR如何控制模式对伴侣或陌生人的神经活动。我们已经在OXTR中产生了载有突变的草原田鼠和V1AR完全消除了这些受体的功能，并开发了光学的方法在行为和大草原中基因表达的行为和基因表达分析过程中自由移动动物的神经活动记录田鼠。使用此功能强大的系统，我们现在可以检验OXTR和V1AR控制不同方面的假设 1）配对纽带和成人社会依恋行为，2）神经的伴侣或陌生人特定模式社交相互作用期间vole大脑的特定区域的活性，以及3）基因表达的变化这些神经种群中的基本社会依恋。我们的初步工作表明OXTR信号是在大草原田径中的配对键合中不需要遗传，因此，对社会依恋基础的神经和分子途径可能会为途径提供新的见解调解如此长期的社会记忆和隶属关系的形成。这些研究将阐明 OXTR和V1AR促进附着并最终告知新治疗的机制在整个精神疾病范围内的方法。