In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse.
In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse.
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DOI：
10.1073/pnas.2117767119
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发表时间：
2022-02-08
影响因子：
11.1
通讯作者：
Lehman MN
中科院分区：
文献类型：
--
作者：
Moore AM;Coolen LM;Lehman MN
下丘脑振荡产生激素分泌的脉动模式，是调节体内平衡系统的基本生理特征。这些神经系统中的单个细胞如何产生和协调偶发性活动和由此产生的脉冲分泌尚不清楚。最近，弓形KNDy （kisspeptin/neurokinin B/dynorphin）细胞被确定为生殖所需的促性腺激素释放激素（GnRH）脉冲发生器的关键组成部分。在自由运动的小鼠中使用KNDy神经元的体内钙成像，我们发现，在每个GnRH脉冲之前，单个KNDy细胞表现出具有惊人时间顺序的同步活动，细胞子集表现为“领导者”或“追随者”。未来的工作将区分这些新的亚群，并确定细胞同步时间顺序的机制，这可能为调节脉冲分泌提供途径。位于弓形核的下丘脑脉冲发生器控制着促性腺激素释放激素（GnRH）和黄体生成素（LH）的间歇性释放，对生殖至关重要。最近的证据表明，该发生器由弓形“KNDy”细胞组成，KNDy是基于kisspeptin， neurokinin B和dynorphin共同表达的缩写。然而，在脉冲期间，缺乏单细胞水平上KNDy神经元活动的直接视觉证据。在这里，我们在自由运动的雌性小鼠中使用体内钙成像来显示单个KNDy神经元以偶发性方式同步激活，并且这些同步的偶发性总是先于LH脉冲。此外，KNDy细胞之间的同步是按时间顺序发生的，在每个同步事件中，KNDy细胞的一些子集充当“领导者”，而其他子集充当“追随者”。这些结果揭示了GnRH脉冲发生器中不可预料的激活和同步的时间组织，表明不同的KNDy神经元亚群在脉冲开始时被激活，而不是在每次脉冲维持和最终终止期间被激活。进一步研究区分KNDy“领导者”和“追随者”细胞可能具有重要的临床意义，因为搏动性GnRH分泌的调节对正常生殖至关重要，在多囊卵巢综合征和下丘脑闭经等病理条件下被破坏。
Hypothalamic oscillators that generate pulsatile patterns of hormone secretion represent a fundamental physiological feature regulating homeostatic systems. How individual cells within these neural ensembles generate and coordinate episodic activity and resultant pulse secretion is unknown. Recently, arcuate KNDy (kisspeptin/neurokinin B/dynorphin) cells were identified as a critical component of the gonadotrophin-releasing hormone (GnRH) pulse generator required for reproduction. Using in vivo calcium imaging of KNDy neurons in freely moving mice, we reveal that, prior to each GnRH pulse, individual KNDy cells demonstrate synchronized activity with striking temporal order, with subsets of cells behaving as “leaders” or “followers.” Future work to distinguish these novel subpopulations and define mechanisms underlying the temporal ordering of cellular synchronization may provide avenues to regulate pulse secretion. A hypothalamic pulse generator located in the arcuate nucleus controls episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) and is essential for reproduction. Recent evidence suggests this generator is composed of arcuate “KNDy” cells, the abbreviation based on coexpression of kisspeptin, neurokinin B, and dynorphin. However, direct visual evidence of KNDy neuron activity at a single-cell level during a pulse is lacking. Here, we use in vivo calcium imaging in freely moving female mice to show that individual KNDy neurons are synchronously activated in an episodic manner, and these synchronized episodes always precede LH pulses. Furthermore, synchronization among KNDy cells occurs in a temporal order, with some subsets of KNDy cells serving as “leaders” and others as “followers” during each synchronized episode. These results reveal an unsuspected temporal organization of activation and synchronization within the GnRH pulse generator, suggesting that different subsets of KNDy neurons are activated at pulse onset than afterward during maintenance and eventual termination of each pulse. Further studies to distinguish KNDy “leader” from “follower” cells is likely to have important clinical significance, since regulation of pulsatile GnRH secretion is essential for normal reproduction and disrupted in pathological conditions such as polycystic ovary syndrome and hypothalamic amenorrhea.
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影响因子：
3.3
作者：
Krajewski, S. J.;Burke, M. C.;Anderson, M. J.;McMullen, N. T.;Rance, N. E.
通讯作者：
Rance, N. E.
影响因子：
56.9
作者：
BELCHETZ, PE;PLANT, TM;KNOBIL, E
通讯作者：
KNOBIL, E
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
4.8
作者：
Han, Su Young;Cheong, Isaiah;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
DOI：
10.1262/jrd.2016-075
发表时间：
2016-10-18
期刊：
The Journal of reproduction and development
影响因子：
--
作者：
Hassaneen A;Naniwa Y;Suetomi Y;Matsuyama S;Kimura K;Ieda N;Inoue N;Uenoyama Y;Tsukamura H;Maeda KI;Matsuda F;Ohkura S
通讯作者：
Ohkura S