Changes in the composition of brain interstitial ions control the sleep-wake cycle.
Changes in the composition of brain interstitial ions control the sleep-wake cycle.
复制标题
DOI：
10.1126/science.aad4821
复制
发表时间：
2016-04-29
期刊：
影响因子：
--
通讯作者：
Nedergaard M
中科院分区：
文献类型：
--
作者：
Ding F;O'Donnell J;Xu Q;Kang N;Goldman N;Nedergaard M
觉醒是由提升的唤醒系统广泛释放的神经调质驱动的。然而，目前还不清楚这些物质如何协调神经元活动中的状态依赖性全局变化。在这里，我们表明，神经调节剂诱导增加细胞外K+浓度（[K+]e）在皮质切片电沉默河豚毒素。在体内，唤醒与AMPA受体无关的[K+]e升高相关，同时伴有[Ca 2 +]e、[Mg 2 +]e、[H+]e和细胞外容积的降低。而自然睡眠和麻醉使[K+]e降低，[Ca ~（2+）]e、[Mg ~（2+）]e、[H+]e增加，细胞外液量增加。睡眠小鼠的局部皮层活动可以很容易地转换为刻板的脑电图模式的觉醒，通过简单地施加细胞外离子组成的变化。因此，细胞外离子控制状态依赖的神经活动模式。
Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e, while increasing [Ca2+]e, [Mg2+]e, [H+]e, as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical EEG pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.