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: 10676011
• 负责人: RICHARD W TSIEN
• 金额: $ 11.23万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10676011
• 关键词: Acceleration; Adult; Affect; Anatomy; Animals; Antibodies; Area; Auditory area; Axon; Behavior; Behavior monitoring; Behavioral; Brain; Caring; Central Nervous System; Child; Child Care; Child Rearing; Childbirth; Clinical; Data; Discipline of Nursing; Foundations; Gender; Hippocampus; Hormones; Knowledge; Maps; Maternal Behavior; Monitor; Mothers; Mus; Neuropeptides; Oxytocin; Oxytocin Receptor; Pair Bond; Parents; Performance; Postpartum Depression; Prosencephalon; Retrieval; Social Behavior; Social Environment; Social Interaction; System; Therapeutic; animal care; autism spectrum disorder; experience; experimental study; gain of function; improved; improved outcome; information processing; loss of function; neglect; neural circuit; optogenetics; public health relevance; pup; receptor; receptor expression; social; social anxiety; social cognition; treatment strategy

Project Summary (Project 1) Oxytocin is a neuropeptide important for social behavior, such as maternal care and pair bonding. It is now believed that direct axonal oxytocin release into various forebrain targets is critical for social behavior, but it remains unclear where and when oxytocin modulation is required to enhance social information processing and regulate maternal behavior. Oxytocin is essential for nursing, but it is unclear what other aspects of maternal behavior by mothers or unrelated co-caring animals depend on the oxytocin system. Oxytocin administration might also be clinically promising, improving outcomes in autism spectrum disorders, social anxiety, and post- partum depression. However, it is imperative to understand the functional anatomy and whole-brain neural circuitry by which oxytocin affects behavioral changes, including when oxytocin might be released, and whether there are differences in oxytocin modulation that depend on gender or social context. Here we will address this critical knowledge gap. Recently, we generated the first specific antibodies to the mouse oxytocin receptor, used these antibodies to determine where these receptors are localized, and examined how oxytocin can enable pup retrieval behavior in maternal mice. Those previous studies provide a robust foundation for the current Project, in which our team aims to understand which target neural circuits are modulated by oxytocin, and if there are behavioral episodes that might be sensitive to oxytocin modulation during brief periods of social interaction. The central hypothesis is that oxytocin is absolutely necessary to initiate maternal behaviors in key areas including auditory cortex and hippocampus, but may be dispensable in experienced mothers. We will perform behavioral, optogenetic, and circuit mapping studies in adult mice to determine where and when oxytocin modulates neural circuits to enhance social information processing and subsequently improve maternal behavior. In Aim 1 we will build a new behavioral recording system to continuously monitor social interactions for days to weeks. In Aim 2, we profile oxytocin projections and oxytocin receptor expression throughout the entire adult brain to find potential hotspots of modulation. Finally in Aims 3 and 4, we perform optogenetic loss-of-function and gain-of-function type experiments to determine where and when oxytocin modulation is needed for maternal behavior or at what points might additional oxytocin release accelerate maternal behavior onset or improve steady-state performance. In summary, here we will study the emergence of social interactions and maternal behaviors as they are naturally expressed during multiple animal co-housing, using a new behavioral monitoring systems we will build. We will then use this system to determine when and where oxytocin modulation is required and most effective at promoting pro-social interactions and child care.

项目摘要（项目1） 催产素是一种对社会行为重要的神经肽，例如孕产妇护理和配对结合。现在 认为直接轴突催产素释放到各种前脑目标中对于社会行为至关重要，但是 尚不清楚需要调节催产素以增强社会信息处理和 调节母性行为。催产素对护理至关重要，但目前尚不清楚孕产妇的其他方面 母亲或无关的共同饲养动物的行为取决于催产素系统。催产素给药 可能在临床上也很有希望，改善了自闭症谱系障碍，社交焦虑和后的结果 组成抑郁症。但是，必须了解功能解剖结构和全脑神经 催产素会影响行为变化的电路，包括何时释放催产素，以及是否是否 催产素的调节存在差异，取决于性别或社会环境。 在这里，我们将解决这个关键的知识差距。最近，我们生成了第一个特异性抗体 小鼠催产素受体使用这些抗体来确定这些受体的局部位置，并且 检查了催产素如何在产妇小鼠中实现幼崽的检索行为。这些先前的研究提供了 当前项目的强大基础，我们的团队旨在了解哪些目标神经回路是 由催产素调节，如果有行为发作可能对催产素调节敏感 短期的社会互动。中心假设是催产素是启动绝对必要的 关键领域的孕产妇行为在内，包括听觉皮层和海马，但在 经验丰富的母亲。我们将在成年小鼠中进行行为，光学遗传学和电路映射研究 确定催产素调节神经回路以增强社会信息处理和 随后改善孕产妇行为。在AIM 1中，我们将建立一个新的行为记录系统 连续监测几天到几周的社交互动。在AIM 2中，我们介绍了催产素的投影和催产素 在整个成年大脑中的受体表达，以找到潜在的调节热点。终于在目标3 和4，我们执行光学遗传丧失功能和功能型类型实验，以确定何处和 当孕产妇行为或在哪些点可能释放催产素时，需要调节催产素 加速孕产妇行为发作或改善稳态表现。 总而言之，我们将在这里研究社会互动和母性行为的出现 自然使用我们将建立的新行为监测系统在多个动物共用期间表达。 然后，我们将使用该系统来确定需要调节催产素的何时何地，并且最有效 促进亲社会互动和儿童保育。