Central synaptic mechanisms regulating ovulation

描述(申请人提供)：促性腺激素释放激素(GnRH)神经元形成调节生殖的最终共同途径。下丘脑节律性释放促性腺激素释放激素刺激垂体促性腺激素的合成和分泌。在女性中，GnRH的释放有大量的激增，这是脑下黄体生成素(LH)激增的最终和先决条件信号，后者随后启动排卵。GnRH的激增依赖于两个信号：卵巢雌二醇水平的上升和来自视交叉上核(SCN)的日常神经信号。解剖学和生理学数据支持血管活性肠肽(VIP)和加压素在SCN向GnRH神经元传递昼夜节律信息中的作用。这项研究的目的是确定GnRH激增发生和时间的神经生物学机制。具体地说，电生理学技术将被用来通过测量GnRH神经元的放电率以及GnRH神经元中的谷氨酸和伽马氨基丁酸(GABA能)突触后电流(PSCs)来探索GnRH神经元功能的变化。对血管活性肠肽和加压素反应的改变将有助于阐明雌二醇反馈效应和每日信号是如何整合的，传递给GnRH神经元，并被GnRH神经元接收，从而适当地调节浪涌。促性腺激素释放激素(GnRH)激增对排卵的绝对要求强调了阐明其发生和时机的确切机制的重要性。

DESCRIPTION (provided by applicant): Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway regulating reproduction. Pulsatile GnRH release from the hypothalamus stimulates synthesis and secretion of pituitary gonadotropins. In females there is a massive surge in GnRH release that serves as the final and prerequisite signal for the pituitary luteinizing hormone (LH) surge, which subsequently initiates ovulation. The GnRH surge is dependent on 2 signals: rising ovarian estradiol levels and a daily neural signal from the suprachiasmatic nuclei (SCN). Anatomical and physiological data support roles for vasoactive intestinal polypeptide (VIP) and vasopressin in the transmission of circadian information from the SCN to GnRH neurons. The goal of this study is to determine the neurobiological mechanisms underlying the generation and timing of the GnRH surge. Specifically, electrophysiological techniques will be used to explore changes in GnRH neuron function in an animal model that exhibits daily LH surges through measurement of GnRH neuron firing rate and glutamatergic and gamma-aminobutyric acid (GABAergic) postsynaptic currents (PSCs) in GnRH neurons. Changes in response to VIP and vasopressin will help elucidate how estradiol feedback effects and the daily signal are integrated, transmitted to, and received by GnRH neurons for the proper regulation of the surge. The absolute requirement of the GnRH surge for ovulation underscores the importance of elucidating the exact mechanisms of its generation and timing.