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.

项目摘要（项目1，共同PI：Froemke、Lin、Buzsaki） 催产素是一种对社会行为很重要的神经肽，如母性关怀，配对和合作 合作伙伴和团体。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， 但目前还不清楚催产素系统是否是异质性的，是否反映了催产素对大脑的重要功能差异。 某些细胞亚群，涉及到动物之间的差异，父母的能力，如果经验依赖的可塑性， 可以使催产素系统适应社交和父母环境。催产素给药也可能是 临床上有望用于自闭症谱系障碍、社交焦虑和产后状况。但据 必须了解催产素释放的哪些方面与养育、合作和社区生活有关， 以及催产素的调节是否因性别、经历或社会背景而存在差异。 在这里，我们将解决这一关键的知识差距。最近，通过U19行为核心，我们建立了一个系统， 用于神经记录和行为监测，在饲养笼上连续收集数天至数月的数据 作为老鼠的父母或共同父母生活在一起。这与体内的照片标记记录相结合， 母体小鼠的催产素神经元。我们的纪录片风格的视频记录揭示了以前未描述的 有经验的母亲似乎鼓励或"教导“共同居住的小狗的行为互动， 天真的处女女性从事母性护理。这些行为激活了Virgin中的光标记催产素细胞 PVN，为当前项目提供了坚实的基础，我们的团队旨在了解哪些方面 由单身母亲、成对母亲和小团体进行的母亲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过渡到养育。中央 一个假设是，催产素系统与幼犬护理和其他人的行为有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 假设这取决于成年人的优势相互作用（与项目2研究和分析）， 计算建模核心），建立有效的共同养育的社会结构。我们会监测催产素 神经元在体内和体外电生理学，光度测定，并执行行为和光/化学遗传 在成年小鼠中进行的研究，以确定催产素何时以及如何调节神经回路以获得社会信息。 处理和可靠的母性行为，调节机制由项目3和相关 在项目2和项目4中确定的用于社会信息处理的脑区。在目标1中，我们研究了初始塑性， 当动物成为单身母亲时，催产素细胞，将催产素细胞放电与筑巢等变量联系起来， 或幼崽体温。在目标2中，我们询问催产素神经元是否有助于有经验的母鼠教导共同居住的天真成年人 共同抚养孩子在目标3中，我们研究了3-4只小鼠（包括有经验的母鼠和窝）的组，以量化动力学 社区生活和共同养育，以及催产素如何帮助确保养育婴儿的社会网络稳定性。