A diverse array of neurometabolic coupling mechanisms exist within the brain to ensure that sufficient metabolite availability is present to meet both acute and chronic energetic demands.

Excitatory synaptic activity, which produces the majority of the brain’s energetic demands, triggers a rapid metabolic response including a characteristic shift towards aerobic glycolysis. Herein, astrocytically derived lactate appears to serve as an important metabolite to meet the extensive metabolic needs of activated neurons. Despite a wealth of literature characterizing lactate’s role in mediating these acute metabolic needs, the extent to which lactate supports chronic energetic demands of neurons remains unclear. We hypothesized that synaptic potentiation, a ubiquitous brain phenomenon that can produce chronic alterations in synaptic activity, could necessitate persistent alterations in brain energetics. In freely-behaving rats, we induced long-term potentiation (LTP) of synapses within the dentate gyrus through high-frequency electrical stimulation (HFS) of the medial perforant pathway. Before, during, and after LTP induction, we continuously recorded extracellular lactate concentrations within the dentate gyrus to assess how changes in synaptic strength alter local glycolytic activity. Synaptic potentiation 1) altered the acute response of extracellular lactate to transient neuronal activation as evident by a larger initial dip and subsequent overshoot and 2) chronically increased local lactate availability. Although synapses were potentiated immediately following HFS, observed changes in lactate dynamics were only evident beginning ~24 h later. Once observed, however, both synaptic potentiation and altered lactate dynamics persisted for the duration of the experiment (~72 h). Persistent alterations in synaptic strength, therefore, appear to be associated with metabolic plasticity in the form of persistent augmentation of glycolytic activity.

大脑内存在各种各样的神经代谢耦合机制，以确保存在足够的代谢物，以满足急性和慢性能量需求。

兴奋性突触活动产生大脑的大部分能量需求，触发快速代谢反应，包括向有氧糖酵解的特征转变。在此，星形胶质细胞来源的乳酸似乎是满足活化神经元广泛代谢需求的重要代谢物。尽管有大量文献描述了乳酸在调节这些急性代谢需求中的作用，但乳酸支持神经元慢性能量需求的程度仍不清楚。我们假设突触增强是一种无处不在的大脑现象，可以产生突触活动的慢性改变，可能需要大脑能量学的持续改变。在行为自由的老鼠中，我们通过内侧穿孔通路的高频电刺激 (HFS) 诱导齿状回内突触的长期增强 (LTP)。在 LTP 诱导之前、期间和之后，我们连续记录齿状回内的细胞外乳酸浓度，以评估突触强度的变化如何改变局部糖酵解活性。突触增强 1) 改变了细胞外乳酸对瞬时神经元激活的急性反应，这可以通过较大的初始下降和随后的过冲来证明，以及 2) 长期增加局部乳酸可用性。尽管在 HFS 后立即增强了突触，但观察到的乳酸动力学变化仅在大约 24 小时后开始才明显。然而，一旦观察到，突触增强和乳酸动力学改变在实验期间（~72 小时）持续存在。因此，突触强度的持续改变似乎与糖酵解活性持续增强形式的代谢可塑性有关。