Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France.
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2013972118.
The hippocampus's dorsal and ventral parts are involved in different operative circuits, the functions of which vary in time during the night and day cycle. These functions are altered in epilepsy. Since energy production is tailored to function, we hypothesized that energy production would be space- and time-dependent in the hippocampus and that such an organizing principle would be modified in epilepsy. Using metabolic imaging and metabolite sensing ex vivo, we show that the ventral hippocampus favors aerobic glycolysis over oxidative phosphorylation as compared to the dorsal part in the morning in control mice. In the afternoon, aerobic glycolysis is decreased and oxidative phosphorylation increased. In the dorsal hippocampus, the metabolic activity varies less between these two times but is weaker than in the ventral. Thus, the energy metabolism is different along the dorsoventral axis and changes as a function of time in control mice. In an experimental model of epilepsy, we find a large alteration of such spatiotemporal organization. In addition to a general hypometabolic state, the dorsoventral difference disappears in the morning, when seizure probability is low. In the afternoon, when seizure probability is high, the aerobic glycolysis is enhanced in both parts, the increase being stronger in the ventral area. We suggest that energy metabolism is tailored to the functions performed by brain networks, which vary over time. In pathological conditions, the alterations of these general rules may contribute to network dysfunctions.
海马体的背侧和腹侧部分参与不同的操作回路，其功能在昼夜周期中随时间而变化。这些功能在癫痫中发生改变。由于能量产生是针对功能量身定制的，我们假设能量产生在海马体中具有空间和时间依赖性，并且这种组织原则在癫痫中会发生改变。使用代谢成像和代谢物体外感应，我们发现在对照小鼠中，与背侧部分相比，腹侧海马体在早晨更倾向于有氧糖酵解而不是氧化磷酸化。下午，有氧糖酵解减少，氧化磷酸化增加。在背侧海马体中，这两种代谢活性之间的变化较小，但比腹侧部分弱。因此，能量代谢沿着背腹轴是不同的，并随时间在对照小鼠中发生变化。在癫痫的实验模型中，我们发现这种时空组织发生了很大的改变。除了普遍的代谢低下状态外，在早晨癫痫发作概率较低时，背腹差异消失。下午，当癫痫发作概率较高时，两个部位的有氧糖酵解均增强，腹侧区域的增强更为明显。我们认为，能量代谢是针对大脑网络执行的功能量身定制的，这些功能随时间而变化。在病理条件下，这些一般规则的改变可能导致网络功能障碍。
