GENES CONTROLLING LORDOSIS BEHAVIOR

描述（申请人摘要）：生殖行为，尤其是 脊柱前凸，已被证明是大脑/行为分析的极好对象。现在对于 如果能辨别出基因对动物行为的影响，雌性老鼠将是理想的选择。 在这里，我们建议研究两个基因：（a）催产素（OT），和（B）其 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，而且在更普遍的联系过程中。作为 OT是一种重要的整合性神经肽，协调某些自然行为 与相应的自主准备。OT神经元，对 脊柱前凸，是战略上方便，位于离散大细胞 下丘脑群这两个基因是如何影响生殖行为的？ I.在分子/生物化学水平上，我们将使用G蛋白分析，包括 新推出的特异性G蛋白敲除小鼠以及反义DNA 技术、OTR拮抗剂和OTR敲除小鼠来测试以下假设： OT通过OTR起作用，激活特定的G蛋白，从而增加 腹内侧下丘脑神经元电活动，从而驱动脊柱前凸 行为二.在行为水平上，我们将使用OT敲除小鼠， 可用的OTR拮抗剂和反义DNA方法以及不 不仅是生殖行为，而且是对压力和焦虑的反应， 探索这两个基因不限于直接影响的假设 脊柱前凸它们能使雌鼠平静下来， 在温和的压力条件下破坏。新颖的“老鼠洞穴系统”将 包括在我们的分析中。作为项目的一部分，我们将解决两个 “谜题”：（i）迄今为止从OT报告的极其微弱的表型 基因敲除：OT基因敲除小鼠如何在哺乳动物中具有如此受限的表型？ 肽的强大的生理和行为作用的看法？(ii)的 OT和加压素之间令人印象深刻的行为差异， 他们的化学相似性：我们在哪里可以解离OT机制， 加压素能帮助解释他们的行为差异吗 总的来说，这项建议继续进行“多层次”调查， 遗传密码的特异性，以分析自然行为 机制等

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.