Intracellular Lactate Dynamics Reveal the Metabolic Diversity of Drosophila Glutamatergic Neurons

Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigate the effects of nutrient deprivation on lactate dynamics in Drosophila glutamatergic neurons by leveraging the limiting effects of the diffusion barrier surrounding cells in culture. We found that neurons constitutively consume lactate when availability of trehalose, the glucose disaccharide preferred by insects, is limited by the diffusion barrier. Acute mechanical disruption of the barrier reduced this reliance on lactate. Through kinetic modeling and experimental validation, we demonstrate that neuronal lactate consumption rates correlate inversely with their mitochondrial density. Further, we found that lactate levels in neurons exhibited temporal correlations that allowed prediction of cytosolic lactate dynamics after the disruption of the diffusion barrier from pre-perturbation lactate fluctuations. Collectively, our findings reveal the influence of diffusion barriers on neuronal metabolic preferences, and demonstrate the existence of temporal correlations between lactate dynamics under conditions of nutrient deprivation and those evoked by the subsequent restoration of nutrient availability.