Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand.
Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10216-E10223. doi: 10.1073/pnas.1713897114. Epub 2017 Nov 6.
The pulsatile release of luteinizing hormone (LH) is critical for mammalian fertility. However, despite several decades of investigation, the identity of the neuronal network generating pulsatile reproductive hormone secretion remains unproven. We use here a variety of optogenetic approaches in freely behaving mice to evaluate the role of the arcuate nucleus kisspeptin (ARN) neurons in LH pulse generation. Using GCaMP6 fiber photometry, we find that the ARN neuron population exhibits brief (∼1 min) synchronized episodes of calcium activity occurring as frequently as every 9 min in gonadectomized mice. These ARN population events were found to be near-perfectly correlated with pulsatile LH secretion. The selective optogenetic activation of ARN neurons for 1 min generated pulses of LH in freely behaving mice, whereas inhibition with archaerhodopsin for 30 min suppressed LH pulsatility. Experiments aimed at resetting the activity of the ARN neuron population with halorhodopsin were found to reset ongoing LH pulsatility. These observations indicate the ARN neurons as the long-elusive hypothalamic pulse generator driving fertility.
黄体生成素 (LH) 的脉冲释放对哺乳动物的生育能力至关重要。然而，尽管经过了几十年的研究，产生脉冲生殖激素分泌的神经元网络的身份仍未得到证实。我们在这里使用各种光遗传学方法在自由活动的小鼠中评估弓状核 kisspeptin (ARN) 神经元在 LH 脉冲产生中的作用。使用 GCaMP6 光纤光度测定法，我们发现 ARN 神经元群体表现出短暂的（约 1 分钟）钙活动同步事件，在去势小鼠中每 9 分钟发生一次。这些 ARN 群体事件与脉冲 LH 分泌几乎完全相关。选择性光遗传学激活 ARN 神经元 1 分钟可在自由活动的小鼠中产生 LH 脉冲，而用 archaerhodopsin 抑制 30 分钟可抑制 LH 脉冲性。旨在用光遗传学重置 ARN 神经元群体活动的实验发现，重置了正在进行的 LH 脉冲性。这些观察结果表明 ARN 神经元是驱动生育能力的长期以来难以捉摸的下丘脑脉冲发生器。
