The gonadotropin-releasing hormone (GnRH) neurons operate as a neuronal ensemble exhibiting coordinated activity once every reproductive cycle to generate the preovulatory GnRH surge. Using GCaMP fibre photometry at the GnRH neuron distal dendrons to measure the output of this widely scattered population in female mice, we find that the onset, amplitude, and profile of GnRH neuron surge activity exhibits substantial variability from cycle to cycle both between and within individual mice. This was also evident when measuring successive proestrous luteinizing hormone surges. Studies combining short (c-Fos and c-Jun) and long (genetic Robust Activity Marking) term indices of immediate early gene activation revealed that, while ∼50% of GnRH neurons were activated at the time of each surge, only half of these neurons had been active during the previous proestrous surge. These observations reveal marked inter- and intra-individual variability in the GnRH surge mechanism. Remarkably, different sub-populations of overlapping GnRH neurons are recruited to the ensemble each estrous cycle to generate the GnRH surge. While engendering variability in the surge mechanism itself, this likely provides substantial robustness to a key event underlying mammalian reproduction.Significance Statement The mid-cycle luteinizing hormone (LH) surge driven by the gonadotropin-releasing hormone (GnRH) neurons represents the key event triggering ovulation in all mammals. Using GCaMP fibre photometry and genetic activation markers, we unexpectedly find that different sub-populations of GnRH neurons are responsible for driving consecutive LH surges every 4-5 days in cycling female mice. This remarkable oscillatory pattern of network plasticity within the ensemble occurs under normal physiological conditions and likely contributes to the variable timing of the onset of LH surge both within and between individuals. The ability of individual GnRH neurons to take turns within the ensemble in driving the LH surge likely provides a robust fail-safe mechanism for ovulation and contributes to the robustness of mammalian fertility.

中文翻译：

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移动的 GnRH 神经元集合是连续排卵前黄体生成素激增的基础。


促性腺激素释放激素 （GnRH） 神经元作为一个神经元集合运作，每个生殖周期表现出一次协调活动，以产生排卵前 GnRH 激增。在 GnRH 神经元远端树突上使用 GCaMP 光纤光度法来测量雌性小鼠中这个广泛分散的群体的输出，我们发现 GnRH 神经元浪涌活动的开始、振幅和概况在个体小鼠之间和内部表现出不同周期之间的显着变化。在测量连续发情前黄体生成素激增时，这一点也很明显。结合即时早期基因激活的短（c-Fos 和 c-Jun）和长（遗传稳健活动标记）术语指数的研究显示，虽然 ∼50% 的 GnRH 神经元在每次发情激增时被激活，但这些神经元中只有一半在之前的发情前激增期间活跃。这些观察揭示了 GnRH 激增机制的个体间和个体内显著差异。值得注意的是，重叠的 GnRH 神经元的不同亚群在每个发情周期被募集到集合中以产生 GnRH 激增。虽然在浪涌机制本身中产生可变性，但这可能为哺乳动物繁殖的关键事件提供了实质性的稳健性。意义陈述由促性腺激素释放激素 （GnRH） 神经元驱动的周期中期黄体生成素 （LH） 激增代表了触发所有哺乳动物排卵的关键事件。使用 GCaMP 纤维光度法和遗传激活标记，我们意外地发现 GnRH 神经元的不同亚群负责在循环雌性小鼠中每 4-5 天驱动一次连续的 LH 激增。 集合内这种显着的网络可塑性的振荡模式发生在正常的生理条件下，并且可能导致个体内部和个体之间 LH 激增发生的可变时间。单个 GnRH 神经元在集合内轮流驱动 LH 激增的能力可能为排卵提供了强大的故障安全机制，并有助于哺乳动物生育能力的稳健性。