Program in Neuroscience, Middlebury College, Middlebury, VT 05753, United States.
Program in Neuroscience, Middlebury College, Middlebury, VT 05753, United States; Department of Psychology, Middlebury College, Middlebury, VT 05753, United States.
Neurobiol Learn Mem. 2020 Nov;175:107314. doi: 10.1016/j.nlm.2020.107314. Epub 2020 Sep 20.
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.
大脑中存在多种神经代谢偶联机制，以确保有足够的代谢物供应来满足急性和慢性能量需求。兴奋性突触活动产生了大脑的大部分能量需求，引发了快速的代谢反应，包括向有氧糖酵解的特征性转变。在此过程中，星形胶质细胞衍生的乳酸似乎是满足激活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，但乳酸在多大程度上支持神经元的慢性能量需求尚不清楚。我们假设，突触增强是一种普遍存在的大脑现象，可以产生突触活动的慢性改变，可能需要持续改变大脑的能量代谢。在自由活动的大鼠中，我们通过对内侧穿通路径进行高频电刺激（HFS）诱导齿状回突触的长时程增强（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短暂神经元激活的急性反应，表现为初始凹陷更大，随后出现过冲；2）慢性增加了局部乳酸的可利用性。尽管在 HFS 后立即增强了突触，但仅在约 24 小时后才观察到乳酸动力学的变化。然而，一旦观察到，突触增强和改变的乳酸动力学持续了整个实验过程（约 72 小时）。因此，突触强度的持续变化似乎与代谢可塑性有关，表现为糖酵解活性的持续增强。
