Neuronal Network Dynamics in the Posterodorsal Amygdala: Shaping Reproductive Hormone Pulsatility
Neuronal Network Dynamics in the Posterodorsal Amygdala: Shaping Reproductive Hormone Pulsatility
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DOI：
10.1101/2024.01.21.574304
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发表时间：
2024-03
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影响因子：
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通讯作者：
Kateryna Nechyporenko;M. Voliotis;Xiao Feng Li;Owen Hollings;D. Ivanova;Jamie J Walker;Kevin T. O’Byrne;Krasimira Tsaneva-Atanasova
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作者：
Kateryna Nechyporenko;M. Voliotis;Xiao Feng Li;Owen Hollings;D. Ivanova;Jamie J Walker;Kevin T. O’Byrne;Krasimira Tsaneva-Atanasova
正常的生殖功能和生育能力依赖于促性腺激素释放激素（GnRH）的节律性分泌，其由下丘脑 GnRH 脉冲发生器驱动。 GnRH 脉冲发生器的关键调节器是内侧杏仁核 (MePD) 的后背亚核，这是一个参与处理外部环境线索（包括压力影响）的大脑区域。然而，能够动态地、应激触发地调节 GnRH 分泌的神经元通路仍然很大程度上未知。在这里，我们采用计算机建模来探索动态输入对 GnRH 脉冲发生器活动的影响。我们介绍并分析了一个代表由 GABA 能和谷氨酸能神经元群体组成的 MePD 神经元回路的数学模型，并将其与我们的 GnRH 脉冲发生器模型集成。我们的分析剖析了兴奋性和抑制性 MePD 投射输出对 GnRH 脉冲发生器活动的影响，并揭示了功能相关的 MePD 谷氨酸投射到 GnRH 脉冲发生器，我们用体内光遗传学对其进行了探测。我们的研究揭示了 MePD 神经元动力学如何影响 GnRH 脉冲发生器活动，并提供了对与压力相关的失调的见解。
Normal reproductive function and fertility rely on the rhythmic secretion of gonadotropin-releasing hormone (GnRH), which is driven by the hypothalamic GnRH pulse generator. A key regulator of the GnRH pulse generator is the posterodorsal subnucleus of the medial amygdala (MePD), a brain region which is involved in processing external environmental cues, including the effect of stress. However, the neuronal pathways enabling the dynamic, stress-triggered modulation of GnRH secretion remain largely unknown. Here, we employ in-silico modelling in order to explore the impact of dynamic inputs on GnRH pulse generator activity. We introduce and analyse a mathematical model representing MePD neuronal circuits composed of GABAergic and glutamatergic neuronal populations, integrating it with our GnRH pulse generator model. Our analysis dissects the influence of excitatory and inhibitory MePD projections’ outputs on the GnRH pulse generator’s activity and reveals a functionally relevant MePD glutamatergic projection to the GnRH pulse generator, which we probe with in vivo optogenetics. Our study sheds light on how MePD neuronal dynamics affect the GnRH pulse generator activity, and offers insights into stress-related dysregulation.