Department of Physiology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2012;7(5):e37909. doi: 10.1371/journal.pone.0037909. Epub 2012 May 23.
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 Ca(2+)/high Mg(2+) 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.
Kisspeptin（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。脊椎动物的下丘脑高度表达 kiss1 和 kisspeptin 受体，低剂量的 kisspeptin 对促性腺激素释放激素-1（GnRH1）神经元动作电位发放率具有强大而持久的刺激作用。鱼类有多种 GnRH 神经元群体，其区别在于它们在大脑中的位置和表达的 GnRH 基因。位于与嗅球相关的终神经（TN）中的 GnRH3 神经元是神经调质，它们不直接参与调节垂体-性腺功能。在斑马鱼中，TN-GnRH3 神经元的电活动受同种鱼视觉线索的调制，被认为是将外部环境信息传递到中枢神经系统的递质。TN-GnRH3 神经元还在性动机和唤醒状态中发挥作用，因此它们是研究协调复杂行为的重要神经元群体。我们研究了 kisspeptin 在调节成年斑马鱼 TN-GnRH3 神经元电活动中的作用。我们在完整大脑准备中使用电生理学方法表明，相对短暂的 100 nM kisspeptin 处理对额外下丘脑 GnRH 神经元群体的电活动具有持久的刺激作用。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发放和用低钙/高镁溶液阻断突触传递抑制了 kisspeptin 对电活动的刺激作用，表明 kisspeptin 通过突触调节间接作用，兴奋 TN-GnRH3 神经元。我们的发现为 kisspeptin 在中枢神经系统中的更广泛功能提供了新的视角，通过其调节参与多种神经调质功能的额外下丘脑 GnRH 神经元。
