Oxytocin modulation of female aggression

催产素调节女性攻击性

• 批准号: 10220159
• 负责人: Dayu Lin
• 金额: $ 46.01万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220159
• 关键词: 3-Dimensional; Address; Affect; Aggressive behavior; Animals; Area; Behavior; Behavioral; Brain; Cells; Data; Distal; Electrophysiology (science); Female; Fiber; Foundations; Gene Expression Profile; Genes; Goals; Hypothalamic structure; In Situ Hybridization; In Vitro; Individual; Infant; Lactation; Maternal Behavior; Measures; Molecular; Monitor; Mothers; Mus; Neurons; Object Attachment; Oxytocin; Oxytocin Receptor; Parents; Partner in relationship; Photometry; Physiological; Play; Population; Postpartum Period; Process; Property; Psychopathology; Role; Signal Transduction; Slice; Social Behavior; Social Interaction; Source; Synapses; System; Testing; Therapeutic; Whole-Cell Recordings; cell type; differential expression; improved; in vivo; insight; male; member; neural circuit; neuromechanism; neuroregulation; novel; optogenetics; pup; receptor; receptor expression; relating to nervous system; response; sensor; small hairpin RNA; social; social attachment; suckling; theories; tool; transcriptome sequencing

Project Summary (Project 4, Co-PIs: Lin, Froemke, Buzsaki, Tsien) Social bonding refers to an intimate relationship formed among members of the same species. Across species, social bonding is often accompanied by increased aggressiveness towards perceived threats against the object of attachment. The neural process underlying the social bonding induced increase in aggression remains unclear. Oxytocin plays pivotal roles in the formation of social bonds. Coincidently, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a hypothalamic region indispensable for both male and female aggression expresses high level of oxytocin receptor and a dense cluster of oxytocin neurons are found right next to the VMHvl. Thus, we hypothesize that oxytocin may play an important role in altering the VMHvl cell responses to potential threat to increase female aggression after mother-infant bonding. Here we will test this hypothesis through three aims. In Aim 1, we will test the functional role of local and distal oxytocin inputs to the VMHvl in increasing female aggression during lactation. In Aim 2, we will perform in vivo cell-type specific recording to address how VMHvl cells and their neighboring oxytocin neurons respond during natural female aggression. Additionally, we will employ a novel genetically encoded oxytocin sensor to address how oxytocin influences the activity of VMHvl cells in naïve and lactating females. In Aim 3, we will employ RNAseq and in vitro slice recording to investigate how the VMHvl cells change the molecular and electrophysiological properties during lactation. In summary, this project will combine the various tools developed in Projects 1-3 to provide new insight into the neuromodulatory mechanisms in hypothalamus that alter aggressive behavior during social bonding.

项目摘要（项目4，Co-Pis：Lin，Fromemke，Buzsaki，Tsien） 社会联系是指同一物种成员之间形成的亲密关系。跨物种， 社会联系通常伴随着对对物体的威胁的侵略性增加 依恋。社会联系引起的侵略性遗体增加的神经过程 不清楚。催产素在社会纽带的形成中起关键作用。巧合的是，腹侧部分 腹侧下丘脑（VMHVL），男性和女性侵略性必不可少的下丘脑区域 表达高水平的氧受体和密集的氧气神经元在旁边发现 VMHVL。这，我们假设氧在改变VMHVL细胞反应中可能起重要作用 母亲结合后，可能会增加女性侵略性的潜在威胁。在这里，我们将检验这个假设 通过三个目标。在AIM 1中，我们将测试局部和盘式氧输入到VMHVL中的功能作用 在AIM 2中，我们将在体内细胞类型的特定记录中执行 介绍VMHVL细胞及其相邻的氧加毒素神经元在天然女性侵略性期间的反应。 此外，我们将采用一种新型的遗传编码氧气传感器来解决氧如何影响氧气 VMHVL细胞在幼稚和泌乳女性中的活性。在AIM 3中，我们将采用RNASEQ和体外切片记录 为了研究VMHVL细胞如何改变泌乳过程中的分子和电生理特性。 总而言之，该项目将结合项目1-3中开发的各种工具，以提供有关该项目的新见解 下丘脑的神经调节机制改变了社会联系期间侵略性行为。