Central synaptic mechanisms regulating ovulation

描述（由申请人提供）：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。下丘脑搏动性释放GnRH刺激垂体促性腺激素的合成和分泌。在女性中，GnRH释放的大量激增作为垂体促黄体激素（LH）激增的最终和先决信号，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每日来自视交叉上核（SCN）的神经信号。解剖和生理数据支持血管活性肠多肽（VIP）和血管加压素在SCN向GnRH神经元传递昼夜节律信息中的作用。本研究的目的是确定GnRH激增的产生和时间的神经生物学机制。具体来说，电生理技术将用于探索动物模型中GnRH神经元功能的变化，该模型通过测量GnRH神经元放电率和GnRH神经元中的谷氨酸能和γ -氨基丁酸（GABAergic）突触后电流（PSCs）来显示每日LH激增。VIP和抗利尿激素反应的变化将有助于阐明雌二醇反馈效应和日常信号如何被整合、传递给GnRH神经元，并被GnRH神经元接收，以正确调节高潮。GnRH激增对排卵的绝对要求强调了阐明其产生和时间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.