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，联合负责人：Lin、Froemke、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感知到的对客体的威胁的攻击性的增加 的附件。社会联系导致攻击性增加的神经过程仍然存在 不清楚。催产素在社会纽带的形成中起着关键作用。巧合的是，腹外侧部分 下丘脑腹内侧区 (VMHvl)，是男性和女性攻击性不可缺少的下丘脑区域 表达高水平的催产素受体，并且在其旁边发现了密集的催产素神经元簇 VMHvl。因此，我们推测催产素可能在改变 VMHvl 细胞对 母婴关系后增加女性攻击性的潜在威胁。在这里我们将检验这个假设 通过三个目标。在目标 1 中，我们将测试 VMHvl 的局部和远端催产素输入的功能作用 增加女性在哺乳期间的攻击性。在目标 2 中，我们将进行体内细胞类型特异性记录 解决 VMHvl 细胞及其邻近的催产素神经元在自然雌性攻击期间如何反应。 此外，我们将采用一种新型基因编码催产素传感器来解决催产素如何影响 幼稚和哺乳期雌性中 VMHvl 细胞的活性。在目标 3 中，我们将采用 RNAseq 和体外切片记录 研究 VMHvl 细胞在哺乳期间如何改变分子和电生理特性。在 总之，该项目将结合项目 1-3 中开发的各种工具，为 下丘脑的神经调节机制改变社会联系期间的攻击行为。