Department of Neurobiology, Stanford University, Stanford, CA, USA.
Department of Applied Physics, Stanford University, Stanford, CA, USA.
Nature. 2021 May;593(7858):244-248. doi: 10.1038/s41586-021-03497-0. Epub 2021 Apr 28.
Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity. However, whether changes in neural activity are causally related to metabolic flux in intact circuits on the timescales associated with behaviour is unclear. Here we combine two-photon microscopy of the fly brain with sensors that enable the simultaneous measurement of neural activity and metabolic flux, across both resting and active behavioural states. We demonstrate that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across brain networks. Using local optogenetic perturbation, we demonstrate that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, which suggests that neuronal metabolism predictively allocates resources to anticipate the energy demands of future activity. Finally, our studies reveal that the initiation of even minimal behavioural movements causes large-scale changes in the pattern of neural activity and energy metabolism, which reveals a widespread engagement of the brain. As the relationship between neural activity and energy metabolism is probably evolutionarily ancient and highly conserved, our studies provide a critical foundation for using metabolic proxies to capture changes in neural activity.
神经元网络的协调活动是许多物种在休息和活跃行为状态下的标志。这些全局模式在数秒到数小时的时间内改变能量代谢，这支持了广泛使用耗氧量和葡萄糖摄取作为神经活动的替代物。然而，在与行为相关的时间尺度上，神经活动的变化是否与完整电路中的代谢通量有因果关系尚不清楚。在这里，我们将果蝇大脑的双光子显微镜与传感器相结合，使我们能够在休息和活跃的行为状态下同时测量神经活动和代谢通量。我们证明神经活动驱动代谢通量的变化，在这些信号之间产生紧密的耦合，可以在整个大脑网络中进行测量。使用局部光遗传学扰动，我们证明即使是短暂的神经活动增加也会导致细胞质 ATP 的快速和持续增加，这表明神经元代谢预测性地分配资源以预测未来活动的能量需求。最后，我们的研究揭示了即使是最小的行为运动的启动也会导致神经活动和能量代谢模式的大规模变化，这揭示了大脑的广泛参与。由于神经活动和能量代谢之间的关系可能是古老而高度保守的，因此我们的研究为使用代谢替代物来捕捉神经活动的变化提供了重要的基础。
