Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.

虽然假设大脑发挥稳态功能以在生理条件下保持细胞能量状态恒定，但这尚未得到实验证明。在这里，我们使用小鼠大脑中的基因编码传感器对主要细胞能量代谢物 5'-三磷酸腺苷 (ATP) 的细胞内浓度进行了体内光学记录。我们证明皮层兴奋性神经元中的细胞内 ATP 水平根据睡眠-觉醒状态以整个皮层的方式波动，与觉醒相关。有趣的是，在快速眼动睡眠期间，ATP 水平显着降低，这表明尽管能量供应的脑血流动力学同时增加，但神经元的能量负平衡。还观察到细胞内 ATP 的减少响应于神经元激活的局部电刺激，而血流动力学同时增强。这些观察结果表明，大脑能量代谢可能并不总是满足神经元能量需求，从而导致神经元细胞内 ATP 水平的生理波动。