Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Department of Mathematics and Living Systems Institute, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK.
J Neuroendocrinol. 2022 Nov;34(11):e13207. doi: 10.1111/jne.13207. Epub 2022 Oct 28.
Kisspeptin neurons in the arcuate nucleus of the hypothalamus generate gonadotrophin-releasing hormone (GnRH) pulses, and act as critical initiators of functional gonadotrophin secretion and reproductive competency. However, kisspeptin in other brain regions, most notably the posterodorsal subnucleus of the medial amygdala (MePD), plays a significant modulatory role over the hypothalamic kisspeptin population; our recent studies using optogenetics have shown that low-frequency light stimulation of MePD kisspeptin results in increased luteinsing hormone pulse frequency. Nonetheless, the neurochemical pathways that underpin this regulatory function remain unknown. To study this, we have utilised an optofluid technology, precisely combining optogenetic stimulation with intra-nuclear pharmacological receptor antagonism, to investigate the neurotransmission involved in this circuitry. We have shown experimentally and verified using a mathematical model that functional neurotransmission of both GABA and glutamate is a requirement for effective modulation of the GnRH pulse generator by amygdala kisspeptin neurons.
下丘脑弓状核中的 kisspeptin 神经元产生促性腺激素释放激素 (GnRH) 脉冲，并作为功能性促性腺激素分泌和生殖能力的关键启动子。然而，其他脑区的 kisspeptin，尤其是内侧杏仁核的后背侧亚核 (MePD)，对下丘脑 kisspeptin 群体起着重要的调节作用；我们最近使用光遗传学的研究表明，MePD kisspeptin 的低频光刺激会增加黄体生成素脉冲频率。尽管如此，支持这种调节功能的神经化学途径仍不清楚。为了研究这一点，我们利用了一种光流技术，精确地将光遗传学刺激与核内药理学受体拮抗作用相结合，以研究该回路中涉及的神经传递。我们已经通过实验证明，并使用数学模型验证，GABA 和谷氨酸的功能性神经传递是杏仁核 kisspeptin 神经元有效调节 GnRH 脉冲发生器的必要条件。
