Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).
Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).
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DOI：
10.1371/journal.pone.0037909
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wayne NL
中科院分区：
文献类型：
--
作者：
Zhao Y;Wayne NL
Kissspeptin(Kiss1基因的产物)是已知的最有效的下丘脑-垂体-性腺轴激活剂。Kiss1和Kisspeptin受体在脊椎动物的下丘脑中都有高表达，低剂量的Kisspeptin对小鼠促性腺激素释放激素-1(GnRH1)神经元的动作电位放电具有强大而持久的刺激作用。鱼类有多个GnRH神经元种群，根据它们在大脑中的位置和它们表达的GnRH基因来区分。位于与嗅球相关的终末神经(TN)的GnRH3神经元是神经调节性的，在调节垂体-性腺功能方面不起直接作用。在青冈鱼中，Tn-GnRH3神经元的电活动受到来自同种生物的视觉提示的调制，被认为是外部环境到中枢神经系统的信息传输器。Tn-GnRH3神经元也在性动机和唤醒状态中发挥作用，使它们成为研究复杂行为协调的重要神经元群体。我们研究了Kispeptin在青竹Tn-GnRH3神经元电活动调节中的作用。在完整的脑准备中使用电生理学，我们表明相对短暂的100 NM的Kispeptin治疗对下丘脑外GnRH神经元的电活动有长期的刺激作用。剂量-反应分析表明，这种神经肽的激活范围相对较窄。此外，用河豚毒素阻断动作电位放电和用低钙/高镁溶液阻断突触传递可抑制Kispeptin对电活动的刺激作用，表明Kispeptin是通过突触调节间接作用于兴奋Tn-GnRH3神经元的。我们的发现提供了一个新的视角，通过调节参与多种神经调节功能的下丘脑外GnRH神经元群，来了解Kispeptin在中枢神经系统中更广泛的功能。
Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca2+/high Mg2+ solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its regulation of an extrahypothalamic population of GnRH neurons involved in multiple neuromodulatory functions.
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作者：
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影响因子：
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