Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ
Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ
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DOI：
10.1523/jneurosci.4925-04.2005
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发表时间：
2005-03-02
影响因子：
5.3
通讯作者：
Verkhratsky, A
中科院分区：
文献类型：
--
作者：
Burdakov, D;Gerasimenko, O;Verkhratsky, A
将身体能量状态的正常变化与调节唤醒和代谢的大脑中心的活动联系起来的生理信号机制还没有得到很好的理解。下丘脑外侧部（LH）的黑色素浓集激素（MCH）和食欲素/下丘脑泌素类型的神经元对唤醒和代谢产生相反的作用。我们研究了脑细胞外葡萄糖的变化，对应于血糖的生理变化是否可以改变神经化学和生物病理学定义的LH细胞在小鼠脑切片的电输出。在这里，我们表明，生理相关浓度的葡萄糖剂量依赖性增强MCH神经元的电兴奋性，诱导去极化和增加膜电阻。我们还表明，葡萄糖的生理变化对食欲素神经元的电活动有相反的影响。我们认为，这些直接行动的葡萄糖的觉醒和代谢调节LH神经元在翻译正常变化的身体能量资源的觉醒和代谢的适当变化中发挥了关键作用。
The physiological signaling mechanisms that link normal variations in body energy status to the activity of arousal- and metabolism-regulating brain centers are not well understood. The melanin-concentrating hormone (MCH) and orexin/hypocretin types of neurons of the lateral hypothalamus (LH) exert opposing effects on arousal and metabolism. We examined whether shifts in brain extracellular glucose that correspond to physiological changes in blood glucose can alter the electrical output of neurochemically and biophysically defined LH cells in mouse brain slices. Here, we show that physiologically relevant concentrations of glucose dose-dependently enhance the electrical excitability of MCH neurons by inducing depolarization and increasing membrane resistance. We also demonstrate that the same physiological shifts in glucose have the opposite effects on the electrical activity of orexin neurons. We propose that these direct actions of glucose on the arousal- and metabolism-regulating LH neurons play a key role in the translation of normal variations in body energy resources into appropriate changes in arousal and metabolism.