Regulation of Reproduction

描述（由申请人提供）：提出的实验的长期目标是确定如何调节生殖的神经控制。具体来说，是什么解剖途径控制着调节生殖系统的细胞和分子行为者。我们将继续使用一个定义良好的硬骨鱼模型系统，在该系统中，我们在受控的实验室条件下模拟自然事件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。我们利用细胞和分子探针和新开发的GnRH转基因动物研究下丘脑-视前区促性腺激素释放激素神经元（GnRH）。单独的环境刺激，取决于它们的价，可以导致含有GnRH的神经元在该物种中体积放大或缩小约8倍。我们最近发现，当动物处于繁殖活跃状态时，GnRH神经元的树突状乔木生长，神经元似乎是耦合的。该系统允许实际的GnRH系统在体内操作，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重要工具。由于GnRH神经元在系统发育上是古老的，并且对所有脊椎动物的生殖控制起着核心作用，因此这些实验将提供有关调节脊椎动物门间生殖的细胞和分子机制的见解。我们将解决几个关于控制生殖能力的细胞和分子变化的关键问题：1)GnRH神经元的树突突是否扩大，在生殖能力强的雄性中介导相互连接，而在生殖能力弱的雄性中收缩，并断开连接？生殖能力强的雄性和生殖能力弱的雄性之间的突触连接在数量和种类上有什么不同？2)生殖能力雄性与非生殖能力雄性的GnRH神经元中有哪些基因表达差异？3)在生殖能力和非生殖能力状态之间的过渡中，哪些脑核是活跃的？它们与GnRH神经元的解剖学联系是什么？4)生殖能力强的雄性和非生殖能力强的雄性的GnRH神经元放电模式不同吗？是什么输入调节了这些放电模式？这项研究的目的是了解控制生殖的神经信号。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认识。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受到调节将有助于改善公众健康。

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.