Wang Luhong, DeFazio Richard A, Moenter Suzanne M
Department of Molecular and Integrative Physiology, University of Michigan , Ann Arbor, MI 48109.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
eNeuro. 2016 Jun 7;3(3). doi: 10.1523/ENEURO.0094-16.2016. eCollection 2016 May-Jun.
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 ERα-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 versus diestrus. Whole-cell recordings were used to study the 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 Ni(2+), suggesting that T-type Ca(2+) currents (I Ts) are involved. I T current density was greater on proestrus versus diestrus. In addition to I T, persistent sodium current (I NaP) facilitated rebound bursting. On diestrus, 4-aminopyridine-sensitive potassium currents contributed to reduced rebound bursts in both tonic and DIB cells. Manipulation of specific sex steroids suggests that 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 versus diestrus by regulating multiple intrinsic currents.
促性腺激素释放激素（GnRH）排卵前的分泌高峰对生育能力至关重要，且受雌二醇反馈作用从负向正的转变所调控。GnRH神经元可能通过表达雌激素受体α（ERα）的传入神经接收雌二醇反馈信号。腹内侧视前核（AVPV）中的 kisspeptin 神经元被认为对 GnRH 高峰的雌二醇正反馈诱导至关重要。我们检查了来自处于动情后期（负反馈）和发情前期（正反馈，高峰时间）的小鼠脑片经绿色荧光蛋白（GFP）鉴定的 AVPV kisspeptin 神经元的电生理特性。细胞外记录显示，与动情后期相比，发情前期的放电频率增加且出现动作电位爆发。采用全细胞记录来研究爆发的内在机制。去极化时，AVPV kisspeptin 神经元表现出紧张性放电或去极化诱导的爆发（DIB）。紧张性放电细胞和 DIB 细胞均表现出由超极化反弹诱导的爆发。DIB 在两个周期阶段的发生情况相似，但发情前期更常观察到反弹爆发。DIB 和反弹爆发均对镍离子（Ni²⁺）敏感，表明 T 型钙电流（I Ts）参与其中。发情前期的 I T 电流密度高于动情后期。除了 I T，持续性钠电流（I NaP）促进了反弹爆发。在动情后期，4-氨基吡啶敏感的钾电流导致紧张性放电细胞和 DIB 细胞中的反弹爆发减少。对特定性类固醇的操作表明，雌二醇诱导了发情前期增强 AVPV kisspeptin 神经元兴奋性的变化。这些观察结果表明，循环雌二醇的周期驱动变化通过调节多种内在电流，增加了发情前期与动情后期相比 AVPV kisspeptin 神经元的整体动作电位产生和爆发放电。
