GENES CONTROLLING LORDOSIS BEHAVIOR

描述(申请人摘要)：生殖行为，尤其是 前凸，已被证明是大脑/行为分析的极好对象。现在，为了 雌性小鼠能够辨别出基因对动物行为的影响，这将是理想的选择。 在这里，我们建议研究两个基因：(A)催产素(OT)和(B)催产素 受体(OTR)。这是一个令人兴奋的系统，不仅涉及生殖 和父母的行为，也在更一般的过程中的联系。AS 作为一种重要的整合神经肽，OT协调某些自然行为 以及它们相应的自主准备。OT神经元，对 前凸，是战略上的便利，位于离散的巨细胞 下丘脑组。这两个基因是如何影响生殖行为的？ I.在分子/生化水平上，我们将使用G蛋白分析，包括 新获得的特异性G蛋白基因敲除小鼠和反义DNA 技术、Otr拮抗剂和Otr基因敲除小鼠来验证这一假设 OT通过OTR工作，激活特定的G-蛋白，从而增加 下丘脑腹内侧神经元的电活动，从而驱动前凸 行为。在行为水平上，我们将使用OT基因敲除小鼠，新的 可用的OTR拮抗剂和反义DNA方法以及检测方法 不仅是生殖行为，还有对压力和焦虑的反应， 探索这两个基因并不局限于直接影响的假设 在前凸方面。它们使雌性老鼠平静下来，并保护生殖行为不受 在压力较小的情况下的干扰。新奇的“老鼠洞穴系统”将 包括在我们的化验中。作为该项目的一部分，我们将解决两个问题 《谜题》：(I)OT迄今报道的令人震惊的弱表型 基因敲除：OT基因敲除小鼠怎么会有如此有限的表型 对多肽强大的生理和行为作用的看法？(Ii) OT和加压素在面对 它们的化学相似性：我们可以从哪里分离OT机制 加压素能帮助解释他们的行为差异吗？ 总体而言，这项提议继续进行一项“多层次”调查，利用 为了分析自然行为，遗传密码的专一性 机械装置。

DESCRIPTION (applicant's abstract): Reproductive behaviors, especially lordosis, have proven excellent subjects for brain/behavior analyses. Now, for discerning genetic influences on animal behavior, female mice will be ideal. Here we propose to study two genes: (a) for oxytocin (OT), and (b) for its receptor (OTR). This is an exciting system, involved not only in reproductive and parental behaviors but also in the more general process of affiliation. As an important integrative neuropeptide, OT coordinates certain natural behaviors with their corresponding autonomic preparations. OT neurons, important for lordosis, are strategically convenient, located in discrete magnocellular hypothalamic groups. How do these two genes influence reproductive behaviors? I. At the molecular/biochemical level, we will use G-protein analyses including newly available specific-G-protein knockout mice as well as antisense DNA techniques, OTR antagonists and OTR knockout mice to test the hypothesis that OT, operating through the OTR, activates specific G-proteins, thus to increase ventromedial hypothalamic neuronal electrical activity, thus to drive lordosis behavior. II. At the behavioral level, we will use OT knockout mice, newly available OTR antagonists and antisense DNA approaches together with assays not only of reproductive behaviors but also of responses to stress and anxiety, to explore the hypothesis that these two genes are not limited to direct effects on lordosis. They calm the female mouse and protect reproductive behaviors from disruption under mildly stressful conditions. Novel "mouse burrow systems" will be included in our assays. As part of the project we will address two "puzzles": (i) the astonishingly weak phenotype reported so far from OT knockouts: How could the OT knockout mouse have such a restricted phenotype in view of the peptide's strong physiological and behavioral roles? (ii) The impressive behavioral differences between OT and vasopressin in the face of their chemical similarities: Where can we dissociate OT mechanisms from vasopressin's in a manner to help explain their behavioral differences? Overall, this proposal continues a "multilevel" investigation which exploits the specificity of the genetic code in order to analyze natural behavioral mechanisms.