Genes Influencing Social Behaviors

描述(由申请人提供)：一种经典的观点声称催产素(OT)促进附属行为，精氨酸加压素(VP)增强攻击性。但很多数据都与此相冲突。这种困惑并不纯粹是由于神经解剖细节、性别或物种造成的。我将使用两种新的方法来比较OT和VP响应系统：(I)使用分子工具和一些新的行为思维；以及(Ii)使用雌激素(E)作为生物相关的探针。为了最大限度地利用遗传知识和初步证据，我们将使用雌性小鼠。具体地说：目标I.我将使用基因敲除技术扰乱OT基因的表达和OT受体--所有有趣的结果都由一种新的反义DNA技术跟进--并测量一种有趣的行为--母性攻击(作为生殖的一部分)，与“从属行为”相比，母性关怀与睾丸素促进的攻击性相比。(我已经证明，半自然环境生活有助于揭示迄今尚未实现的行为表型。)目的II.这些系统的雌激素调节为探索与E相关的新分子工具提供了机会。ER基因敲除小鼠、反义寡核苷酸、选择性激动剂和拮抗剂是否会改变上述三种行为？目的III.将在正常妊娠和哺乳期小鼠身上验证该项目的主要发现。在所有目标中，分子操作的重要目标将在杏仁核：基底外侧核参与恐惧；中央核参与焦虑；中等皮质区域参与信息素信号传递。所有这些功能都会影响本项目中测量的三种行为。 同样重要的是：背侧视前区负责母性行为，背侧中缝负责5-羟色胺和攻击性。这个项目利用了我的实验室和洛克菲勒大学校园的多学科能力，并以“如果/然后”的风格来展示我们将如何最大限度地发挥5年工作的影响。这些实验将增加我们对两个极其重要的转录系统OT和VP的理解，它们具有广泛的投射和显著的自主神经和行为影响。影响：催产素可能与产后抑郁症有关。OT系统当然有助于社会识别，这种障碍在自闭症和精神分裂症中尤为突出。

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.