GABAergic Transmission to Kisspeptin Neurons Is Differentially Regulated by Time of Day and Estradiol in Female Mice
GABAergic Transmission to Kisspeptin Neurons Is Differentially Regulated by Time of Day and Estradiol in Female Mice
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DOI：
10.1523/jneurosci.3057-14.2014
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发表时间：
2014-12-03
影响因子：
5.3
通讯作者：
Moenter, Suzanne M.
中科院分区：
文献类型：
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作者：
DeFazio, Richard A.;Elias, Carol F.;Moenter, Suzanne M.
促性腺激素释放激素（GnRH）的分泌受雌二醇反馈调节。在女性中，这种反馈从负面转变为正面；对于许多物种来说，这种转变取决于一天中的时间。雌二醇反馈可能通过传入神经传递。弓状核和前腹侧-室周区 (AVPV) 的 Kisspeptin 神经元可能分别在负反馈和正反馈期间差异调节 GnRH 神经元。我们使用带有 GFP 识别的 Kisspeptin 神经元的转基因小鼠测试了雌二醇和一天中 GABA 能传递的时间调节以及对 GABA 的突触后反应。在AM（负反馈）或PM（正反馈）中研究接受或未接受雌二醇（E）治疗的卵巢切除（OVX）小鼠。 GABAA 受体逆转电位不受时间或雌二醇的影响。 GABA 去极化 OVX + E 小鼠弓形神经元的膜电位；这种反应在 OVX 小鼠的细胞中减弱。 GABA 使 AVPV Kisspeptin 神经元超极化，但 OVX PM 组除外，其中 GABA 不会因 PM 基线膜电位超极化而改变膜电位。在 OVX 小鼠的两个 Kisspeptin 神经元群体中，GABA 能自发突触后电流的频率在 PM 中增加；这种增加被雌二醇所抑制。在弓状神经元中，但在 AVPV 中，雌二醇可降低微型突触后电流幅度，而与一天中的时间无关。使用非平稳波动分析和安定来操纵 GABA(A) 受体表观亲和力，弓形微型突触后电流幅度的降低归因于 GABA 结合的受体数量减少。因此，一天中的时间和雌二醇反馈都针对突触前和突触后机制，通过 GABA 能传递差异调节 Kisspeptin 神经元。
Gonadotropin-releasing hormone (GnRH) secretion is regulated by estradiol feedback. This feedback switches from negative to positive in females; this switch depends on time of day in many species. Estradiol feedback is likely conveyed via afferents. Kisspeptin neurons of the arcuate nucleus and anteroventral-periventricular region (AVPV) may differentially regulate GnRH neurons during negative and positive feedback, respectively. We tested estradiol and time of day regulation of GABAergic transmission and postsynaptic response to GABA in these two populations using transgenic mice with GFP-identified kisspeptin neurons. Ovariectomized (OVX) mice treated or not with estradiol (E) were studied in the AM (negative feedback) or PM (positive feedback). GABAA receptor reversal potential was unaffected by time of day or estradiol. GABA depolarized the membrane potential of arcuate neurons from OVX + E mice; this response was blunted in cells from OVX mice. GABA hyperpolarized AVPV kisspeptin neurons, except in the OVX PM group in which GABA did not alter membrane potential attributable to a PM hyperpolarization of baseline membrane potential. In both kisspeptin neuron populations from OVX mice, the frequency of GABAergic spontaneous postsynaptic currents was increased in the PM; this increase was blunted by estradiol. In arcuate, but not AVPV, kisspeptin neurons, estradiol reduced miniature postsynaptic current amplitude independent of time of day. Using nonstationary fluctuation analysis and diazepam to manipulate GABA(A) receptor apparent affinity, the decrease in arcuate miniature postsynaptic current amplitude was attributed to decreased number of receptors bound by GABA. Time of day and estradiol feedback thus both target presynaptic and postsynaptic mechanisms to differentially regulate kisspeptin neurons via GABAergic transmission.