Central synaptic mechanisms regulating ovulation

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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.