%0 Journal Article %A Luhong Wang %A Richard A. DeFazio %A Suzanne M. Moenter %T Excitability and burst generation of AVPV kisspeptin neurons are regulated by the estrous cycle via multiple conductances modulated by estradiol action %D 2016 %R 10.1523/ENEURO.0094-16.2016 %J eneuro %P ENEURO.0094-16.2016 %X The preovulatory secretory surge of gonadotropin-releasing hormone (GnRH) is crucial for fertility and is regulated by a switch of estradiol feedback action from negative to positive. GnRH neurons likely receive estradiol feedback signals via ERĪ±-expressing afferents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV) are thought to be critical for estradiol positive feedback induction of the GnRH surge. We examined the electrophysiological properties of GFP-identified AVPV kisspeptin neurons in brain slices from mice on the afternoon of diestrus (negative feedback) and proestrus (positive feedback, time of surge). Extracellular recordings revealed increased firing frequency and action potential bursts on proestrus vs. diestrus. Whole-cell recordings were used to study intrinsic mechanisms of bursting. Upon depolarization, AVPV kisspeptin neurons exhibited tonic firing or depolarization-induced bursts (DIB). Both tonic and DIB cells exhibited bursts induced by rebound from hyperpolarization. DIB occurred similarly on both cycle stages, but rebound bursts were observed more often on proestrus. DIB and rebound bursts were both sensitive to Ni2+, suggesting T-type Ca2+ currents (IT) are involved. IT current density was greater on proestrus vs. diestrus. In addition to IT, persistent sodium current, INaP, facilitated rebound bursting. On diestrus, 4-aminopyridine (4-AP)-sensitive potassium currents contributed to reduced rebound bursts in both tonic and DIB cells. Manipulation of specific sex steroids suggests estradiol induces the changes that enhance AVPV kisspeptin neuron excitability on proestrus. These observations indicate cycle-driven changes in circulating estradiol increased overall action potential generation and burst firing in AVPV kisspeptin neurons on proestrus vs. diestrus by regulating multiple intrinsic currents.Significance Statement: The brain controls fertility via the hypothalamo-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) neurons form the final output pathway but are not directly sensitive to critical elements of gonadal steroid feedback. Kisspeptin neurons of the anteroventral periventricular nucleus may convey steroid feedback to GnRH neurons. We studied how action potential firing of kisspeptin neurons varies between two critical phases of the estrous cycle: diestrus when estradiol exerts negative feedback to suppress GnRH release, and proestrus when estradiol feedback activates GnRH neurons. Increased spontaneous and burst firing on proestrus were observed and attributable to estrous-cycle dependent changes in multiple ionic currents. These changes were specifically driven by estradiol. This estrous-cycle regulation of kisspeptin neuron excitability is likely a critical aspect of female fertility. %U https://www.eneuro.org/content/eneuro/early/2016/05/18/ENEURO.0094-16.2016.full.pdf