Genes Influencing Social Behaviors

影响社会行为的基因

• 批准号: 6963418
• 负责人: Donald W. Pfaff
• 金额: $ 33.8万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963418
• 关键词: aggression; amygdala; antisense nucleic acid; arginine vasopressin; behavior test; behavioral /social science research tag; behavioral genetics; estrogen receptors; estrogens; ethology; gene expression; gene targeting; genetically modified animals; hormone receptor; hormone regulation /control mechanism; laboratory mouse; lactation; maternal behavior; neurochemistry; oxytocin; pregnancy; sex behavior

DESCRIPTION (provided by applicant): A classical view claims that oxytocin (OT) fosters affiliative behaviors and arginine vasopressin (VP) enhances aggression. But a lot of data conflict with this. The confusion is not due purely to neuroanatomical details, or gender or species. I will use two novel approaches to compare OT and VP responsive systems: (I.) Using molecular tools and some new behavioral thinking; and (II.) Using estrogens (E) as biologically relevant probes. In order to take maximal advantage of genetic knowledge and preliminary evidence we will use female mice. Specifically: Aim I. I will perturb OT gene expression and OT receptors using gene knockouts - with all interesting results followed up by a novel antisense DNA technique - and measure an interesting behavior maternal aggression (as part of reproduction), compared to an 'affiliative behavior', maternal care compared to testosterone-facilitated aggression. (I have already shown that seminatural environment living helps to reveal hitherto unrealized behavioral phenotypes.) Aim II. Estrogenic regulations of these systems offer the opportunity to probe with novel E-related molecular tools. Will ER gene knockout mice, antisense oligos, and selective agonists and antagonists change the three behaviors above in the predicted directions? Aim III. Will verify major discoveries of this project in normal pregnant and lactating mice. In all Aims, important targets for molecular manipulations will be in the amygdala: The basolateral nuclei are involved in fear; the central nucleus in anxiety; and the mediocortical region in signaling by pheromones. All of these functions could influence the three behaviors measured in this project. Also important: The dorsolateral preoptic area for maternal behavior, and the dorsal raphe for serotonin and aggression. This project uses the multidisciplinary capacity of my laboratory and the Rockefeller University campus, and is written in an "if/then" style to show how we will maximize the impact of 5 years of work. These experiments will increase our understanding of two extremely important transcriptional systems, OT and VP, with widespread projections and significant autonomic and behavioral effects. Impact: OT may be involved in postpartum depression. OT systems certainly facilitate social recognition, disorders of which are prominent in autism and in schizophrenia.

描述（由申请人提供）：一种经典的观点声称催产素（OT）促进了隶属行为和精氨酸加压素（VP）增强了侵略性。 但是许多数据冲突。 混乱并非纯粹归因于神经解剖学细节或性别或物种。 我将使用两种新颖的方法来比较OT和VP响应系统：（I。）使用分子工具和一些新的行为思维； （ii。）使用雌激素（E）作为生物学相关的探针。 为了获得遗传知识和初步证据的最大优势，我们将使用雌性小鼠。 具体：AIM I。我将使用基因敲除基因表达和OT受体扰动 - 所有有趣的结果随后进行了一种新型的反义DNA技术，并与“隶属行为”相比，与孕妇护理相比，与测试蛋白蛋白酶相比，测量了有趣的行为母体侵略（作为生殖行为的一部分）。 （我已经表明，半自然的环境生活有助于揭示迄今未实现的行为表型。）AIM II。 这些系统的雌激素法规为使用新型的电子相关分子工具提供了探测的机会。 ER基因基因敲除小鼠，反义寡聚以及选择性激动剂和拮抗剂会在预测的方向上改变上述三种行为吗？ 目标三。 将验证正常怀孕和哺乳小鼠中该项目的主要发现。 在所有目的中，分子操作的重要靶标将在杏仁核中：基底外侧核与恐惧有关；焦虑中的中央核；以及信息素信号传导中的地皮区域。 所有这些功能都可能影响该项目中测得的三种行为。 同样重要的是：孕产妇行为的背外侧前区域，以及5-羟色胺和侵略性的背侧raphe。 该项目使用我的实验室和洛克菲勒大学校园的跨学科能力，并以“ if/then”风格编写，以表明我们将如何最大程度地提高5年工作的影响。 这些实验将提高我们对两个非常重要的转录系统OT和VP的理解，并具有广泛的投影以及显着的自主神经和行为效应。 影响：OT可能参与产后抑郁症。 OT系统肯定会促进社会认可，其疾病在自闭症和精神分裂症中是突出的。