Oxytocin Modulation of Neural Circuit Function and Behavior

项目摘要 催产素是一种从下丘脑合成和释放的多肽荷尔蒙，用于生殖、母体护理、 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”荷尔蒙，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交注意力，即放大或使人们能够选择性地注意 某些社会刺激，如婴儿哭闹的声音或威胁或地位较高的人的出现 个人的。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 该系统承诺改善各种精神障碍的社会缺陷，如自闭症。尽管人们热情高涨 对于催产素来说，催产素在改善人类社会行为方面的有效性一直存在矛盾的结果 据报道。文献中的这种不一致很可能是因为我们对催产素作用的复杂性缺乏了解， 这可能会随着行为状态、经验和大脑结构的不同而不同。我们相信，更好的理解 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 保守的神经肽。推进我们的理解需要跨层次和比较跨学科的 具有重叠兴趣和分析催产素的技术能力的一组研究人员进行的研究 跨分子、生理、系统行为和水平的信号。这包括多种动物之间的相互作用， 因为许多精神障碍会对社会行为、整个生命周期和整个大脑产生影响。 为此，这位在纽约大学格罗斯曼医学院提出的U19研究课题是《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 根据他们作为管理、行为、计算建模、数据科学和分子工具的职责 核心。四个项目和核心的首要目标是更好地理解催产素 通过开发新的工具和理论来调节社会空间行为，我们将其定义为 在特定环境或行为环境中的社会互动。我们的团队将联合起来，共同应对 来源(催产素神经元)和接受端(表达催产素受体)的催产素系统 神经元)。对于总体目标1，项目1和2询问不同群体的催产素神经元如何促进稳定 成人社会等级制度，延伸到集体育儿，以确保后代的生存是一个关键优势 一个稳定的社会生态系统。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 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，以开发影响社会空间的特定电路扰动的方法 在多时空尺度上的学习。总体目标4是确保学生、博士后和工作人员 团队成员得到良好的指导，并在支持社会的环境中进行这些研究。

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.