Regulation of Reproduction

描述（由申请人提供）：所提出的实验的长期目标是确定生殖的神经控制是如何调节的。具体来说，什么样的解剖途径控制细胞和分子的演员，调节生殖系统。我们将继续使用一个定义明确的硬骨鱼模型系统，在该系统中，我们在模拟自然事件的受控实验室条件下操纵动物的生殖状态，并测量已识别神经元的细胞和分子后果。我们专注于促性腺激素释放激素神经元（GnRH）在下丘脑视前区使用细胞和分子探针和一个新开发的GnRH转基因动物。单独的环境刺激，取决于它们的效价，可以导致含有GnRH的神经元放大或缩小约100。8-在这个物种中的体积是原来的两倍。我们最近发现，当动物繁殖活跃时，GnRH神经元的树突状乔木生长，神经元似乎是耦合的。该系统允许GnRH系统的真实体内操纵，为发现外部信号如何调节大脑及其细胞和分子过程提供了必要的工具。由于GnRH神经元在遗传学上是古老的，并且对所有脊椎动物的生殖控制至关重要，因此这些实验将提供关于调节脊椎动物门生殖的细胞和分子机制的见解。我们将解决几个关键问题的细胞和分子的变化，负责控制生殖能力：1）GnRH神经元的树突状乔木扩大，介导的相互连接在生殖能力的男性和收缩，并断开生殖能力低下的男性？有生殖能力的雄性和无生殖能力的雄性之间的突触连接在数量和种类上有何不同？2)哪些基因在有生殖能力的男性与无生殖能力的男性的GnRH神经元中差异表达？3)哪些脑核团在生殖能力和非生殖能力状态之间的转换中是活跃的，它们与GnRH神经元的解剖学联系是什么？4)有生殖能力和无生殖能力的男性之间GnRH神经元的放电模式是否不同？什么样的输入调节这些放电模式？公共卫生相关性这项研究旨在了解是什么神经信号控制生殖。发现大脑如何控制生殖将扩展我们对这一关键生理过程的了解。由于健康的生殖系统对生殖成功至关重要，因此更多地了解生殖如何调节将有助于改善公共卫生。

DESCRIPTION (provided by applicant): The long term goal of the experiments proposed is to identify how neural control of reproduction is regulated. Specifically, what anatomical pathways control cellular and molecular actors that regulate the reproductive system. We will continue using a well defined teleost fish model system in which we manipulate the reproductive status of animals under controlled laboratory conditions mimicking natural events and measure the cellular and molecular consequences in identified neurons. We focus on gonadotropin-releasing hormone neurons (GnRH) in the hypothalamic-preoptic area using cellular and molecular probes and a newly developed GnRH transgenic animal. Environmental stimuli alone, depending on their valence, can cause GnRH containing neurons to enlarge or shrink ca. 8-fold in volume in this species. We have recently discovered that when animals are reproductively active, the dendritic arbors of GnRH neurons grow and the neurons appear to be coupled. This system allows realistic in vivo manipulation of the GnRH system providing an essential tool for discovering how external signals regulate the brain and its cellular and molecular processes. Since GnRH neurons are phylogenetically ancient and central to the control of reproduction in all vertebrates, these experiments will provide insight about the cellular and molecular mechanisms regulating reproduction across vertebrate phyla. We will address several key questions about the cellular and molecular changes responsible for controlling reproductive competence: 1) Do dendritic arbors of GnRH neurons enlarge, mediating interconnections in reproductively competent males and shrink, and disconnect in reproductively incompetent males? How are the synaptic connections different in number and kind between reproductively competent and incompetent males? 2) What genes are differentially expressed in GnRH neurons of reproductively competent males versus non-competent males? 3) What brain nuclei are active in the transition between reproductively competent and non- competent states and what are their anatomical connections to the GnRH neurons? 4) Are the GnRH neuronal firing patterns different between reproductively competent and non- competent males? What inputs regulate these firing patterns? PUBLIC HEALTH RELEVANCE This research is directed at understanding what neural signals control reproduction. Discovering how the brain controls reproduction will extend our knowledge of this critical physiological process. Since a healthy reproductive system is critically important for reproductive success, greater knowledge of how reproduction is regulated will contribute to better public health.