Oxytocin Modulation of Neural Circuit Function and Behavior

催产素对神经回路功能和行为的调节

• 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
• 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

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.

项目摘要 催产素是一种由下丘脑合成和释放的肽类激素，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。 虽然有时被称为“信任”激素，但越来越多的证据表明， 表明催产素可以增加社会显着性，即，放大或使选择性注意力， 某些社会刺激，如婴儿哭泣的声音或威胁或高地位的存在， 单独的.催产素被认为具有治疗潜力，催产素进入中枢神经系统后， 该系统有望改善各种精神障碍的社会缺陷，如自闭症。尽管热情高涨 对于催产素，催产素在改善人类社会行为方面的功效的矛盾结果已经被 报道文献中的这种不一致性可能是由于我们对催产素作用的复杂性理解不足， 这可能会随着行为状态、经验和大脑结构而变化。我们认为，更好地了解 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。 保守神经肽推进认识需要跨层次、跨学科的比较研究 一组研究人员的研究，他们的兴趣和技术能力重叠，分析催产素 跨分子、生理、系统行为和水平的信号传导。这包括多动物的相互作用， 因为许多精神障碍对社会行为、整个生命周期和整个大脑都有影响。 为此，纽约大学格罗斯曼医学院的U19提出了“催产素调节 神经回路功能与行为”由四个相互关联的项目和五个核心设施组成， 管理、行为、计算建模、数据科学和分子工具 丹四个项目和核心的首要目标是更好地理解催产素 通过发展新的工具和理论来调节社会空间行为，我们将其定义为 在特定的背景或行为环境中的社会互动。我们的团队将联手解决 催产素系统从源头（催产素神经元）和接收端（催产素受体表达 神经元）。对于总体目标1，项目1和项目2询问不同的催产素神经元群体如何促进稳定的催产素神经元。 成年人的社会等级制度，延伸到集体养育，以确保后代的生存作为一个关键的优势 稳定的社会生态系统。对于总体目标2，项目3深入到详细的细胞，突触和微电路 调节催产素作用的机制。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，开发特定电路扰动影响社会空间的方法 在多个时空尺度上学习总体目标4是确保学生，博士后和工作人员 小组成员得到良好的指导，并在一个支持性的亲社会环境中进行这些研究。