In Vivo Recordings of GnRH Neuron Firing Reveal Heterogeneity and Dependence upon GABAA Receptor Signaling
In Vivo Recordings of GnRH Neuron Firing Reveal Heterogeneity and Dependence upon GABAA Receptor Signaling
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DOI：
10.1523/jneurosci.0533-13.2013
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发表时间：
2013-05-29
影响因子：
5.3
通讯作者：
Herbison, Allan E.
中科院分区：
文献类型：
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作者：
Constantin, Stephanie;Iremonger, Karl J.;Herbison, Allan E.
促性腺激素释放激素（GnRH）神经元是所有哺乳动物调节生育的关键细胞。这些神经元的分散分布使得研究它们的性质变得极其困难，而记录它们在体内的电活动的关键目标几乎是不可能的。GnRH神经元连续体的尾端延伸使一些细胞非常接近大脑底部的下丘脑前部区域。由此，我们在麻醉的GnRH- gfp小鼠中开发了一种实验程序，可以在体内记录这些GnRH神经元的电活动。细胞上的记录显示，大多数GnRH神经元（86%）自发地活跃，表现出一系列的放电模式，尽管只有少数（15%）表现出突发放电。平均放电频率范围为0.06至3.65 Hz，最常见的脉冲间隔时间接近500 ms。所有GnRH神经元均被AMPA和kisspeptin激活。GABA(A)受体激动剂muscimol对GnRH神经元放电产生兴奋性、抑制性或混合作用，而GABAA受体拮抗剂picrotoxin对GnRH神经元放电产生一致的抑制作用。这些观察结果代表了体内GnRH神经元的第一次电记录。他们发现体内GnRH神经元的放电模式具有相当大的异质性，与体外放电既有相似之处，也有不同之处。体内这些可变的放电模式被发现严重依赖于正在进行的GABAA受体信号传导。
The gonadotropin-releasing hormone (GnRH) neurons are the key cells regulating fertility in all mammalian species. The scattered distribution of these neurons has made investigation of their properties extremely difficult and the key goal of recording their electrical activity in vivo near impossible. The caudal-most extension of the GnRH neuron continuum brings some cells very close to the base of the brain at the level of the anterior hypothalamic area. Taking insight from this, we developed an experimental procedure in anesthetized GnRH-GFP mice that allows the electrical activity of these GnRH neurons to be recorded in vivo. On-cell recordings revealed that the majority of GnRH neurons (86%) were spontaneously active, exhibiting a range of firing patterns, although only a minority (15%) exhibited burst firing. Mean firing frequencies ranged from 0.06 to 3.65 Hz, with the most common interspike interval being similar to 500 ms. All GnRH neurons tested were activated by AMPA and kisspeptin. Whereas the GABA(A) receptor agonist muscimol evoked excitatory, inhibitory, or mixed effects on GnRH neuron firing, the GABAA receptor antagonist picrotoxin resulted in a consistent suppression of firing. These observations represent the first electrical recordings of GnRH neurons in vivo. They reveal that GnRH neurons in vivo exhibit considerable heterogeneity in their firing patterns with both similarities and differences to firing in vitro. These variable patterns of firing in vivo are found to be critically dependent upon ongoing GABAA receptor signaling.