Changes in GABAergic Transmission to and Intrinsic Excitability of Gonadotropin-Releasing Hormone (GnRH) Neurons during the Estrous Cycle in Mice.
Changes in GABAergic Transmission to and Intrinsic Excitability of Gonadotropin-Releasing Hormone (GnRH) Neurons during the Estrous Cycle in Mice.
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DOI：
10.1523/eneuro.0171-18.2018
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发表时间：
2018-09
期刊：
影响因子：
3.4
通讯作者：
Moenter SM
中科院分区：
文献类型：
--
作者：
Adams C;Chen X;Moenter SM
促性腺激素释放激素（GnRH）神经元形成控制生育的最终共同中枢输出通路，并受类固醇反馈调节。在女性中，雌二醇的反馈作用在负反馈和正反馈之间变化;负反馈通常调节GnRH的间歇性释放，而正反馈则启动GnRH的激增，随后促黄体生成素（LH）的释放最终触发排卵。在发情周期中，雌激素负反馈和正反馈之间的变化随着周期阶段和一天中的时间而发生，在夜间物种中，在发情前期的下午晚些时候出现正反馈。为了验证GnRH神经元的突触和内在特性受周期阶段和一天中的时间调节的假设，我们在两个时间段进行了小鼠脑片中GnRH神经元的全细胞膜片钳研究，认为是负反馈（动情前期PM和动情间期PM）和正反馈期间（动情前期PM）。GABA能传递可以兴奋GnRH神经元，并且在来自动情前期PM小鼠的细胞中高于来自动情前期AM小鼠的细胞，并且接近相对于来自动情间期PM小鼠的细胞的传统显著水平。动作电位反应电流注射也更大的细胞从动情前期PM小鼠比其他两组。有趣的是，动情前期AM的激素环境对GnRH神经元兴奋性和GABA能突触后电流（PSC）幅度的负反馈作用比动情间期PM强。这些观察结果表明，GnRH神经元的突触和内在特性的元素以周期依赖的方式进行调节，并提供了深入了解神经内分泌功能的状态之间的雌二醇负反馈和正反馈的周期性变化的神经生物学机制。
Gonadotropin-releasing hormone (GnRH) neurons form the final common central output pathway controlling fertility and are regulated by steroid feedback. In females, estradiol feedback action varies between negative and positive; negative feedback typically regulates episodic GnRH release whereas positive feedback initiates a surge of GnRH, and subsequently luteinizing hormone (LH) release ultimately triggering ovulation. During the estrous cycle, changes between estradiol negative and positive feedback occur with cycle stage and time of day, with positive feedback in the late afternoon of proestrus in nocturnal species. To test the hypotheses that synaptic and intrinsic properties of GnRH neurons are regulated by cycle stage and time of day, we performed whole-cell patch-clamp studies of GnRH neurons in brain slices from mice at two times considered negative feedback (diestrous PM and proestrous AM) and during positive feedback (proestrous PM). GABAergic transmission can excite GnRH neurons and was higher in cells from proestrous PM mice than cells from proestrous AM mice and approached traditional significance levels relative to cells from diestrous PM mice. Action potential response to current injection was also greater in cells from proestrous PM mice than the other two groups. Interestingly, the hormonal milieu of proestrous AM provided stronger negative feedback on both GnRH neuron excitability and GABAergic postsynaptic current (PSC) amplitude than diestrous PM. These observations demonstrate elements of both synaptic and intrinsic properties of GnRH neurons are regulated in a cycle-dependent manner and provide insight into the neurobiological mechanisms underlying cyclic changes in neuroendocrine function among states of estradiol negative and positive feedback.