Spontaneous Kisspeptin Neuron Firing in the Adult Mouse Reveals Marked Sex and Brain Region Differences but No Support for a Direct Role in Negative Feedback
Spontaneous Kisspeptin Neuron Firing in the Adult Mouse Reveals Marked Sex and Brain Region Differences but No Support for a Direct Role in Negative Feedback
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DOI：
10.1210/en.2012-1616
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发表时间：
2012-11-01
期刊：
影响因子：
4.8
通讯作者：
Herbison, Allan E.
中科院分区：
文献类型：
--
作者：
de Croft, Simon;Piet, Richard;Herbison, Allan E.
Kisspeptin-Gpr 54信号传导对于控制生育的GnRH神经元网络至关重要。本研究报告的kisspeptin（吻）-绿色荧光蛋白（GFP）的小鼠模型，使脑切片电生理记录从吻神经元的弓状核（ARN）和第三脑室（RP 3V）的嘴侧室周区。使用双重免疫荧光，约90%的GFP细胞在RP 3V的女性，和ARN在两种性别，被证明是真实的吻合成神经元在成年小鼠。ARN Kiss-GFP细胞的细胞贴附记录揭示了它们的平均放电率的显著性别差异;雄性中90%的Kiss-GFP细胞表现出缓慢的不规则放电（0.17 +/- 0.04 Hz），而来自间情期（0.01 +/- 0.01 Hz）和卵巢切除（0 Hz）小鼠的神经元大多数或完全沉默。相反，RP 3V Kiss-GFP细胞都是自发活性的，表现出紧张性、不规则和爆发性放电模式。动情间期的平均放电频率（2.1 +/-0.3 Hz）显著高于卵巢切除的小鼠（1.0 +/-0.2 Hz），而放电模式没有任何变化。记录从RP 3V Kiss-GFP神经元在动情前期的GnRH激增的时间显示了一个显着的下降，放电率激增后。总之，这些观察结果表明，意想不到的性别差异的电活动的ARN吻神经元和显着不同的模式，由吻神经元在ARN和RP 3V的发射。虽然数据支持性腺类固醇对RP 3V Kiss神经元放电的积极影响，但没有发现直接证据支持先前假设的ARN Kiss神经元在雌激素负反馈机制中的作用。（内分泌学153：5384-5393，2012）
Kisspeptin-Gpr54 signaling is critical for the GnRH neuronal network controlling fertility. The present study reports on a kisspeptin (Kiss)-green fluorescent protein (GFP) mouse model enabling brain slice electrophysiological recordings to be made from Kiss neurons in the arcuate nucleus (ARN) and rostral periventricular region of the third ventricle (RP3V). Using dual immunofluorescence, approximately 90% of GFP cells in the RP3V of females, and ARN in both sexes, are shown to be authentic Kiss-synthesizing neurons in adult mice. Cell-attached recordings of ARN Kiss-GFP cells revealed a marked sex difference in their mean firing rates; 90% of Kiss-GFP cells in males exhibited slow irregular firing (0.17 +/- 0.04 Hz) whereas neurons from diestrous (0.01 +/- 0.01 Hz) and ovariectomized (0 Hz) mice were mostly or completely silent. In contrast, RP3V Kiss-GFP cells were all spontaneously active, exhibiting tonic, irregular, and bursting firing patterns. Mean firing rates were significantly (P < 0.05) higher in diestrus (2.1 +/- 0.3 Hz) compared with ovariectomized (1.0 +/- 0.2 Hz) mice without any changes in firing pattern. Recordings from RP3V Kiss-GFP neurons at the time of the proestrous GnRH surge revealed a significant decline in firing rate after the surge. Together, these observations demonstrate unexpected sex differences in the electrical activity of ARN Kiss neurons and markedly different patterns of firing by Kiss neurons in the ARN and RP3V. Although data supported a positive influence of gonadal steroids on RP3V Kiss neuron firing, no direct evidence was found to support the previously postulated role of ARN Kiss neurons in the estrogen-negative feedback mechanism. (Endocrinology 153:5384-5393, 2012)