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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：
10438587
负责人：
RICHARD W TSIEN
金额：
$ 275.17万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10438587
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

项目摘要

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.

催产素是一种肽激素，由下丘脑合成并释放，用于生殖和母体行为。最近的研究将催产素标记为一种“信任”激素，有望改善社会缺陷各种精神障碍，例如自闭症。尽管人们对催产素充满热情，但研究结果却相互矛盾催产素在改善人类社会行为方面的功效已有报道。文学中的这种矛盾是可能是由于我们对催产素作用的复杂性了解甚少，而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，更好地了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。推进我们的理解需要一组研究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来分析分子、生理、系统行为和级别。这包括多动物互动，因为许多精神障碍都会产生影响影响整个生命周期和整个大脑的社会行为。催产素对母体大脑的作用尤其明显重要的是，它代表了催产素在社会背景下最古老和最重要的功能。为此，纽约大学医学院拟议的“催产素调节”大脑倡议项目神经回路功能和行为”由四个相互关联的项目和四个核心设施组成，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目标了解社会空间行为中催产素的调节，我们将其定义为内部的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的问题源头（催产素神经元）和接收端（表达催产素受体的神经元）项目1和2将解决连通性、行为影响、体内反应、释放和体验—— 催产素神经元的依赖性变化。从接收端开始，项目 3 将深入研究详细的蜂窝网络，介导催产素作用的突触和微电路机制。最后，项目 4 将结合从项目 1、2 和 3 开发的知识和技术，用于研究状态依赖性催产素调节攻击行为所必需的大脑部位，即大脑的腹外侧部分下丘脑腹内侧区（VMHvl）。有趣的是，在 VMHvl 附近发现了一组催产素神经元，尽管目前尚不清楚其行为相关性，但可能提供催产素的本地来源。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来提供对母亲社会空间行为的神经回路的深入描述。