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: 10220151
• 负责人: RICHARD W TSIEN
• 金额: $ 272.88万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220151
• 关键词: Address; Advisory Committees; Affect; Aggressive behavior; Animals; Antibodies; Antibody Formation; Archives; Area; BRAIN initiative; Behavior; Behavior Control; Behavioral; Biological; Biophysics; Brain; Brain Diseases; Cells; Collaborations; Communication; Communities; Core Facility; Data Analyses; Data Science Core; Development; Ensure; Environment; Equilibrium; Exocytosis; Female; Fostering; Goals; Hippocampus (Brain); Hormones; Human; Hypothalamic structure; Infrastructure; Interdisciplinary Study; International; Investigation; Knowledge; Literature; Logic; Longevity; Maternal Behavior; Mediating; Mental disorders; Mentors; Methods; Modeling; Molecular; Monitor; Mus; Neuronal Plasticity; Neurons; Neuropeptides; Occupational activity of managing finances; Optical Methods; Oxytocin; Oxytocin Receptor; Physiological; Population; Postdoctoral Fellow; Procedures; Production; Reporting; Reproduction; Research; Research Personnel; Research Project Grants; Resolution; Resource Sharing; Resources; Role; Schedule; Schizophrenia; Signal Transduction; Site; Social Behavior; Social Environment; Social Interaction; Source; Spatial Behavior; Structure; Students; Synapses; Synaptic Transmission; Synaptic plasticity; System; Techniques; Testing; Therapeutic; Time; Training; Trust; United States National Institutes of Health; Vesicle; autism spectrum disorder; behavior influence; cognitive function; comparative; data management; experience; flexibility; functional outcomes; high school; improved; in vivo; information processing; interdisciplinary approach; interest; male; maternal aggression; medical schools; meetings; multidisciplinary; neural circuit; neuronal circuitry; neuronal excitability; neuroregulation; next generation; novel; optogenetics; peptide hormone; receptive field; response; social cognition; social deficits; spatial memory; success; symposium; theories; tool; undergraduate student; volunteer

Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a “trust” hormone, promising 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 a 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. Oxytocin action in maternal brain is especially important as it represents the most ancient and important function of oxytocin under a social context. To these ends, the proposed Brain Initiative Project in NYU School of Medicine on “Oxytocin Modulation of Neural Circuit Function and Behavior” consists of four inter-related Projects and four Core facilities, including an Administrative Core, a Data Science Core, a Behavioral Optogenetics Core, and an Oxytocin Receptor Antibody Production Core. The overarching goal of the four Projects and the Cores is to achieve a better understanding of the oxytocin modulation in socio-spatial behaviors, 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) From the source, Project 1 and 2 will address the connectivity, behavioral influence, in vivo responses, release and experience- dependent changes of the oxytocin neurons. From the receiving ends, Project 3 will dive into detailed cellular, synaptic and microcircuit mechanisms that mediate the oxytocin actions. Lastly, Project 4 will combine the knowledge and techniques developed from Projects 1, 2, and 3 to investigate the state-dependent oxytocin modulation of aggressive behaviors at a brain site essential for aggression, the ventrolateral part of the ventromedial hypothalamus (VMHvl). Intriguingly, a group of oxytocin neurons are found neighboring the VMHvl, potentially providing a local source of oxytocin although its behavioral relevance is currently unknown. Together these Projects and Cores develop new tools, use cutting-edge techniques, and large-scale methods to provide an in-depth description of the neural circuitry for maternal socio-spatial behavior.

催产素是一种由下丘脑合成和释放的肽类激素，用于生殖和母体 行为最近的研究将催产素标记为“信任”激素，有望改善社交缺陷， 各种精神疾病，如自闭症。尽管人们对催产素很感兴趣， 已经报道了催产素在改善人类社会行为中的功效。文学中的这种矛盾是 这可能是由于我们对催产素作用的复杂性理解不足，催产素作用可能随行为状态而变化， 经验和大脑结构。我们相信，更好地理解催产素的内源性作用是 释放这种高度进化保守的神经肽的治疗潜力的关键。推进我们 理解需要一组调查人员进行跨层次和跨学科的比较研究， 重叠的兴趣和技术能力，分析催产素信号在分子，生理， 系统行为和水平。这包括多动物的相互作用，因为许多精神障碍是有影响的 对社会行为的影响，在整个生命周期和整个大脑中。催产素在母体大脑中的作用尤其 因为它代表了催产素在社会背景下最古老和最重要的功能。 为了达到这些目的，纽约大学医学院提出的关于“催产素调节”的大脑倡议项目 神经回路功能与行为研究”由四个互相关连的项目及四个核心设施组成，包括 行政核心、数据科学核心、行为光遗传学核心和催产素受体 抗体生产核心。四个项目和核心的总体目标是实现更好的 理解催产素在社会空间行为中的调节，我们将其定义为社会互动， 特定的背景或行为环境。我们的团队将联手解决催产素系统， 源（催产素神经元）和接收端（催产素受体表达神经元）从源， 项目1和2将解决连接，行为影响，体内反应，释放和经验- 催产素神经元的依赖性变化。从接收端，项目3将深入到详细的蜂窝， 介导催产素作用的突触和微电路机制。最后，项目4将联合收割机 从项目1、2和3中开发的知识和技术，以研究状态依赖性催产素 在对攻击性至关重要的大脑部位，即大脑皮层的腹外侧部分， 腹内侧下丘脑（VMHvl）。有趣的是，在VMHvl附近发现了一组催产素神经元， 潜在地提供催产素的局部来源，尽管其行为相关性目前是未知的。一起 这些项目和核心开发新工具，使用尖端技术和大规模方法，以提供 对母亲社会空间行为的神经回路的深入描述。