Definition of the hypothalamic GnRH pulse generator in mice
Definition of the hypothalamic GnRH pulse generator in mice
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DOI：
10.1073/pnas.1713897114
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发表时间：
2017-11-21
影响因子：
11.1
通讯作者：
Herbison, Allan E.
中科院分区：
文献类型：
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作者：
Clarkson, Jenny;Han, Su Young;Herbison, Allan E.
黄体生成素 (LH) 的脉冲式释放对于哺乳动物的生育能力至关重要。然而，尽管进行了数十年的研究，产生脉动生殖激素分泌的神经元网络的身份仍未得到证实。我们在自由行为的小鼠中使用多种光遗传学方法来评估弓状核 Kisspeptin (ARN(KISS)) 神经元在 LH 脉冲生成中的作用。使用 GCaMP6 光纤光度测定法，我们发现 ARN(KISS) 神经元群体表现出短暂（类似于 1 分钟）的钙活动同步发作，在性腺切除小鼠中每 9 分钟发生一次。发现这些 ARN(KISS) 群体事件与脉动 LH 分泌几乎完全相关。 ARN(KISS) 神经元的选择性光遗传学激活 1 分钟会在自由行为的小鼠中产生 LH 脉冲，而古视紫红质抑制 30 分钟则抑制 LH 脉动。旨在用盐视紫红质重置 ARN(KISS) 神经元群活动的实验发现，可以重置正在进行的 LH 搏动。这些观察结果表明 ARN(KISS) 神经元是驱动生育能力的长期难以捉摸的下丘脑脉冲发生器。
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(KISS)) neurons in LH pulse generation. Using GCaMP6 fiber photometry, we find that the ARN(KISS) neuron population exhibits brief (similar to 1 min) synchronized episodes of calcium activity occurring as frequently as every 9 min in gonadectomized mice. These ARN(KISS) population events were found to be near-perfectly correlated with pulsatile LH secretion. The selective optogenetic activation of ARN(KISS) 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(KISS) neuron population with halorhodopsin were found to reset ongoing LH pulsatility. These observations indicate the ARN(KISS) neurons as the long-elusive hypothalamic pulse generator driving fertility.