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，Co-Pis：Fromemke，Lin，Buzsaki） 催产素是一种对社会行为重要的神经肽，例如母校护理，配对和合作 由合作伙伴和团体。直接轴突氧释放到各种前脑目标中对于社会行为至关重要， 但是目前尚不清楚氧加毒素系统是否是异质的，并且反映了重要的功能差异 某些细胞子集与父母能力的动物间差异有关，如果依赖经验的可塑性 可以使氧气系统适应社会和父母的环境。催产素给药也可能是 自闭症谱系障碍，社交焦虑和产后疾病的临床前景。但是，是 必须了解氧气释放的哪些方面与育儿，合作和社区生活有关， 以及取决于性，经验或社会环境的催产素调节是否存在差异。 在这里，我们将解决这个关键的知识差距。最近，使用U19行为核心，我们构建了一个系统 对于神经元记录和行为监测，在家庭笼子中连续收集数据 作为老鼠父母或共同父母的生活。这与已鉴定的体内的光标记录音结合 母亲小鼠中的催产素神经元。我们的纪录片风格的视频录制揭示了先前所描述的 经验丰富的母亲似乎鼓励或也许“教”共同开设的小狗的行为互动 - 幼稚的处女女性从事孕产妇护理。这些行为激活了Virgin中的光标记的催产素细胞 PVN，为当前项目提供了强大的基础，我们的团队旨在了解哪些方面 单个母亲，对和小组的母亲护理 - 激活氧加毒素神经元需要氧加毒素 信号传导，并可能在过渡到育儿后产生或取决于该系统的可塑性。中央 假设是催产素系统与与幼犬护理有关的社会变量和其他 潜在的共同父母，以调节单​​个和共同父母的行为以确保幼犬的存活率。我们进一步 假设这取决于成人的优势相互作用（对项目2进行了研究，并用 计算建模核心）建立了有效共同育儿的社会结构。我们将监测催产素 具有体内和体外电生理学，光度法并进行行为和选择性/化学基因的神经元 在成年小鼠中的研究以确定氧气何时以及如何调节神经回路以获取社会信息 处理和可靠的母性行为，并具有项目3告知的调制机制和相关的 在项目2和4中确定的社会信息处理的大脑区域。在目标1中，我们研究的初始可塑性 催产素细胞当动物成为单身母亲时，将催产素细胞发射与变量相关的变量 或幼犬温度。在AIM 2中，我们询问氧气神经元是否有助于经验丰富的大坝教授共同幼稚的成年人 共同父母。在AIM 3中，我们研究了3-4只小鼠（包括经验丰富的大坝和升）组以量化动态 共同生活和共同育儿，以及氧气如何有助于确保社交网络稳定养育婴儿。