Functional organization and plasticity of the oxytocin system for single or communal parenting in mice

小鼠单亲或共同养育催产素系统的功能组织和可塑性

• 批准号: 10705987
• 负责人: Robert Crooks Froemke
• 金额: $ 64.97万
• 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/10705987
• 关键词: Adult; Aggressive behavior; Animals; Area; Attention; Axon; Behavior; Behavior monitoring; Behavioral; Behavioral Sciences; Birth; Brain; Brain region; Caring; Cells; Child Care; Child Rearing; Clinical; Computer Models; Cues; Data; Data Science Core; Educational process of instructing; Electrophysiology (science); Ensure; Environment; Evaluation; Female; Foundations; Funding; Genetic study; Home; Hypothalamic structure; In Vitro; Infant; Infrastructure; Knowledge; Lactation; Lead; Learning; Life; Maternal Behavior; Maternal Physiology; Methods; Modeling; Molecular; Monitor; Mothers; Mus; Neurons; Neuropeptides; Oxytocin; Pair Bond; Parents; Partner in relationship; Pattern; Performance; Peripheral; Photometry; Physiological; Postpartum Period; Pregnancy; Prosencephalon; Rewards; Siblings; Signal Transduction; Single Parent; Social Behavior; Social Dominance; Social Environment; Social Interaction; Social Network; Spatial Behavior; Survival Rate; System; Temperature; Time; Video Recording; Work; autism spectrum disorder; behavior change; cell type; commune; experience; experimental study; improved; in vivo; information processing; male; motherhood; neglect; neural; neural circuit; offspring; paraventricular nucleus; pup; recruit; sex; social; social anxiety; social structure; supraoptic nucleus; theories; tool

Project Summary (Project 1, Co-PIs: Froemke, Lin, Buzsaki) Oxytocin is a neuropeptide important for social behavior, such as maternal care, pair bonding, and cooperation by partners and groups. Direct axonal oxytocin release into various forebrain targets is critical for social behavior, but it remains unclear if the oxytocin system is heterogeneous and reflects important functional differences for certain cell subsets, relates to inter-animal differences in parental abilities, and if experience-dependent plasticity can adapt the oxytocin system to social and parental environments. Oxytocin administration might also be clinically promising for autism spectrum disorders, social anxiety, and post-partum conditions. However, it is imperative to understand what aspects of oxytocin release relate to parenting, cooperating, and communal living, and whether there are differences in oxytocin modulation that depend on sex, experience, or social context. Here we will address this critical knowledge gap. Recently, with the U19 Behavior Core we built a system for neural recordings and behavioral monitoring, continuously collecting data over days to months on home cage life as mice parent or co-parent together. This was combined with photo-tagged recordings in vivo of identified oxytocin neurons in maternal mice. Our documentary-style video recordings revealed previously-undescribed behavioral interactions by which experienced mothers seemed to encourage or perhaps ‘teach’ co-housed pup- naïve virgin females to engage in maternal care. These behaviors activated photo-tagged oxytocin cells in virgin PVN, providing a robust foundation for the current Project, in which our team aims to understand what aspects of maternal care- by single mothers, pairs, and small groups- activate oxytocin neurons, require oxytocin signaling, and might produce or depend on plasticity of this system upon transition to parenting. The central hypothesis is that the oxytocin system is attuned to social variables related to pup care and the behavior of other potential co-parents, to regulate the behavior of single and co-parents to assure pup survival. We further hypothesize that this depends on adult dominance interactions (studied with Project 2 and analyzed with the Computational Modeling Core) that set up social structures for effective co-parenting. We will monitor oxytocin neurons with in vivo and in vitro electrophysiology, photometry, and perform behavioral and opto-/chemo-genetic studies in adult mice to determine when and how oxytocin modulates neural circuits for social information processing and reliable maternal behavior, with mechanisms of modulation informed by Project 3 and relevant brain areas for social information processing identified in Projects 2 and 4. In Aim 1 we study initial plasticity of oxytocin cells when animals become single mothers, relating oxytocin cell firing to variables such nest building or pup temperature. In Aim 2, we ask if oxytocin neurons help experienced dams teach co-housed naive adults to co-parent. In Aim 3, we study groups of 3-4 mice (including an experienced dam and litter) to quantify dynamics of communal living and co-parenting, and how oxytocin helps ensure social network stability for raising infants.

项目总结(项目1，共同绩效指标：Froemke，Lin，Buzsaki) 催产素是一种对社会行为很重要的神经肽，如母爱、夫妻关系和合作 按合作伙伴和团体分类。轴突催产素直接释放到各种前脑靶点对社会行为至关重要， 但目前尚不清楚催产素系统是否是异质性的，是否反映了重要的功能差异 某些细胞亚群，与动物间亲代能力的差异有关，以及是否依赖经验的可塑性 可以使催产素系统适应社会和父母环境。催产素的使用也可能是 在治疗自闭症谱系障碍、社交焦虑和产后疾病方面有临床应用前景。然而，它是 必须了解催产素释放的哪些方面与育儿、合作和公共生活有关， 以及催产素的调节是否存在取决于性别、经历或社会背景的差异。 在这里，我们将解决这一关键的知识差距。最近，我们用U19行为核心构建了一个系统 用于神经记录和行为监测，在家中笼子上连续收集数天至数月的数据 作为老鼠父母或共同父母一起生活。这与在活体内识别的光标记记录相结合 母鼠体内的催产素神经元。我们之前披露的纪录片风格的视频记录-未描述 有经验的母亲似乎通过行为互动来鼓励或教育同居的幼崽-- 天真的处女去从事母性护理。这些行为激活了处女体内的光标记催产素细胞 PVN，为当前项目提供了坚实的基础，我们团队的目标是了解哪些方面 由单亲母亲、双亲和小团体进行的产妇护理激活催产素神经元，需要催产素 信号，并可能产生或依赖于这个系统的可塑性在过渡到育儿。中环 假设催产素系统与与幼犬照料和其他动物行为相关的社会变量相协调。 潜在的共同父母，以规范单亲和共同父母的行为，以确保幼崽的生存。我们进一步 假设这取决于成虫的优势交互作用(用项目2研究，用 计算建模核心)，为有效的共同育儿建立社会结构。我们会监测催产素 神经元在体内和体外的电生理学，光度学，并执行行为和光/化学发生 在成年小鼠身上进行的研究，以确定催产素何时以及如何调节社会信息的神经回路 处理和可靠的母亲行为，以及项目3和相关的调制机制 在项目2和4中确定了用于社会信息处理的大脑区域。在目标1中，我们研究了 动物成为单亲母亲时催产素细胞，催产素细胞激活与筑巢等变量的关系 或者幼崽的体温。在目标2中，我们询问催产素神经元是否有助于有经验的水坝教导合住的幼稚成年人。 共同为人父母。在目标3中，我们研究了3-4只小鼠(包括一只经验丰富的母鼠和一窝小鼠)，以量化动力学。 共同生活和共同育儿，以及催产素如何帮助确保养育婴儿的社会网络稳定。