Oxytocin Modulation of Neural Circuit Function and Behavior

催产素对神经回路功能和行为的调节

基本信息

批准号：
10705986
负责人：
RICHARD W TSIEN
金额：
$ 486.29万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705986
关键词：
Achievement Adult Affect Animals Area BRAIN initiative Behavior Behavior Control Behavioral Biological Biophysics Brain Brain Diseases Brain region Caring Central Nervous System Child Rearing Collaborations Communication Communities Complex Computer Models Core Facility Crying Data Science Data Science Core Decision Making Development Ecosystem Ensure Environment Extramural Activities Fostering Funding Goals Hippocampus Hormones Human Hypothalamic structure Image Individual Infant Interdisciplinary Study Investments Ion Channel Knowledge Lateral Lead Learning Literature Longevity Mediating Memory Mental disorders Mentors Methods Molecular Mus Neuronal Plasticity Neurons Neuropeptides Output Oxytocin Oxytocin Receptor Pattern Peripheral Physiological Physiological Processes Population Postdoctoral Fellow Property Reagent Reporting Reproduction Research Personnel Research Project Grants Schizophrenia Signal Transduction Social Behavior Social Dominance Social Hierarchy Social Interaction Social Network Source Spatial Behavior Stimulus Structure Students Synapses Synaptic Transmission Synaptic plasticity System Techniques Testing Therapeutic Training Trust United States National Institutes of Health Work animal data autism spectrum disorder career development cognitive function commune comparative data curation experience fitness flexibility functional outcomes improved in vivo innovation interdisciplinary approach interest medical schools member multidisciplinary neural neural circuit neuronal excitability neuroregulation next generation offspring peptide hormone public health relevance repository selective attention social social deficits social learning social relationships sound spatiotemporal success supportive environment theories tool

项目摘要

Project Summary Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction, maternal care, and social behavior, as well as various ‘non-social’ aspects of internal state and physiological processes. Although sometimes referred to as a ‘trust’ hormone, a growing body of evidence across species and brain areas indicates that oxytocin can increase social salience, i.e., amplifying or enabling selective attention towards certain social stimuli, such as the sound of a crying infant or the presence of a threatening or high-status individual. Oxytocin is believed to have therapeutic potential, and delivery of oxytocin into the central nervous system promises to improve social deficits in various mental disorders, such as autism. Despite the enthusiasm for oxytocin, contradictory results in the efficacy of oxytocin in improving human social behaviors have been reported. Such inconsistency in literature is likely due to our poor understanding of complexity of oxytocin action, which likely varies with behavioral state, experience and brain structures. We believe that a better understanding of the endogenous action of oxytocin is the key to unleash the therapeutic potential of this highly evolutionary conserved neuropeptide. Advancing our understanding requires cross-level and comparative inter-disciplinary studies by an group of investigators with overlapping interests and the technical capability to analyze oxytocin signaling across molecular, physiological, systems behavioral and levels. This includes multi-animal interactions, as many mental disorders are impactful on social behavior, over the lifespan and throughout the brain. To these ends, this proposed U19 at NYU Grossman School of Medicine on “Oxytocin Modulation of Neural Circuit Function and Behavior” consists of four inter-related Projects and five Core facilities, designated by their responsibilities as Administrative, Behavior, Computational Modeling, Data Science, and Molecular Tools Cores. The overarching goal of the four Projects and Cores is to achieve a better understanding of the oxytocin modulation in socio-spatial behaviors through the development of new tools and theories, which we define as social interactions within a specific context or behavioral environment. Our team will join forces to tackle the oxytocin system from both the source (oxytocin neurons) and the receiving ends (oxytocin receptor-expressing neurons). For Overall Aim 1, Projects 1 and 2 ask how different populations of oxytocin neurons promote stable adult social hierarchy, extending to collective parenting to ensure the survival of offspring as one key advantage of a stable social ecosystem. For Overall Aim 2, Project 3 dives into detailed cellular, synaptic and microcircuit mechanisms that mediate the oxytocin actions. In Overall Aim 3, Project 4 combines knowledge and techniques developed from Projects 1, 2, and 3 to develop methods for specific circuit perturbations to affect socio-spatial learning over multiple spatio-temporal scales. Overall Aim 4 is to ensure that the students, postdocs, and staff team members receive good mentoring and conduct these studies in a supportive pro-social environment.

项目概要催产素是一种肽激素，由下丘脑合成并释放，用于生殖、产妇护理、和社会行为，以及内部状态和生理过程的各种“非社会”方面。尽管有时被称为“信任”激素，但越来越多的跨物种和大脑区域的证据表明催产素可以增加社会显着性，即放大或启用对某些社会刺激，例如婴儿哭泣的声音或威胁或地位高的人的存在催产素被认为具有治疗潜力，并将催产素输送到中枢神经系统。尽管人们热情高涨，但该系统有望改善各种精神障碍（例如自闭症）的社会缺陷。对于催产素，催产素在改善人类社会行为方面的功效存在矛盾的结果据报道，文献中的这种不一致可能是由于我们对催产素作用的复杂性了解不足。我们相信，这可能会随着行为状态、经验和大脑结构的不同而有所不同。催产素的内源性作用是释放这种高度进化的治疗潜力的关键促进我们对保守神经肽的理解需要跨层次和跨学科的比较。由一组具有重叠兴趣和分析催产素技术能力的研究人员进行的研究跨分子、生理、系统行为和水平的信号传导，包括多动物相互作用、因为许多精神障碍都会影响整个生命周期和整个大脑的社会行为。为此，纽约大学格罗斯曼医学院的 U19 提出了“催产素调节神经回路功能和行为”由四个相互关联的项目和五个核心设施组成，指定为按其管理、行为、计算建模、数据科学和分子工具的职责四个项目和核心的总体目标是更好地了解催产素。通过开发新工具和理论来调节社会空间行为，我们将其定义为我们的团队将齐心协力解决特定背景或行为环境中的社交互动。催产素系统来自源头（催产素神经元）和接收端（表达催产素受体）对于总体目标 1，项目 1 和 2 询问不同的催产素神经元群体如何促进稳定。成人社会等级制度，延伸到集体养育，以确保后代的生存为一项关键优势对于总体目标 2，项目 3 深入研究了详细的细胞、突触和微电路。在总体目标 3 中，项目 4 结合了知识和技术。从项目 1、2 和 3 发展而来，用于开发特定电路扰动影响社会空间的方法总体目标 4 是确保学生、博士后和工作人员能够在多个时空尺度上进行学习。团队成员得到良好的指导，并在支持性的亲社会环境中进行这些研究。