Ding Fengfei, O'Donnell John, Xu Qiwu, Kang Ning, Goldman Nanna, Nedergaard Maiken
Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Science. 2016 Apr 29;352(6285):550-5. doi: 10.1126/science.aad4821.
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 [Ca(2+)]e, [Mg(2+)]e, [H(+)]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K(+)]e while increasing [Ca(2+)]e, [Mg(2+)]e, and [H(+)]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.
觉醒由上行唤醒系统广泛释放神经调质所驱动。然而，尚不清楚这些物质如何协调神经元活动中依赖状态的全局变化。在此，我们表明神经调质可诱导被河豚毒素电沉默的皮质切片中细胞外钾离子浓度（[K⁺]e）升高。在体内，觉醒与不依赖AMPA受体的[K⁺]e升高相关，同时[Ca²⁺]e、[Mg²⁺]e、[H⁺]e及细胞外体积降低。相反，自然睡眠和麻醉会降低[K⁺]e，同时增加[Ca²⁺]e、[Mg²⁺]e、[H⁺]e以及细胞外体积。通过简单改变细胞外离子组成，可轻易将睡眠小鼠的局部皮质活动转换为典型的觉醒脑电图模式。因此，细胞外离子控制着依赖状态的神经活动模式。
