Oligodendrocytes in the Mouse Corpus Callosum Maintain Axonal Function by Delivery of Glucose

In the optic nerve, oligodendrocytes maintain axonal function by supplying lactate as an energy substrate. Here, we report that, in acute brain slices of the mouse corpus callosum, exogenous glucose deprivation (EGD) abolished compound action potentials (CAPs), which neither lactate nor pyruvate could prevent. Loading an oligodendrocyte with 20 mM glucose using a patch pipette prevented EGD-mediated CAP reduction in about 70% of experiments. Loading oligodendrocytes with lactate rescued CAPs less efficiently than glucose. In mice lacking connexin 47, oligodendrocyte filling with glucose did not prevent CAP loss, emphasizing the importance of glial networks for axonal energy supply. Compared with the optic nerve, the astrocyte network in the corpus callosum was less dense, and loading astrocytes with glucose did not prevent CAP loss during EGD. We suggest that callosal oligodendrocyte networks provide energy to sustain axonal function predominantly by glucose delivery, and mechanisms of metabolic support vary across different white matter regions. [Display omitted] •Aglycemia abolishes compound action potentials (CAPs) in the corpus callosum•Lactate perfusion is unable to rescue callosal CAPs during aglycemia•Filling single oligodendrocytes with glucose rescues axonal function during aglycemia•Coupled glial networks are a prerequisite for this rescue Meyer et al. find that, unlike in the optic nerve, lactate does not substitute for glucose to sustain axonal function in the mouse corpus callosum. Oligodendrocyte networks in the corpus callosum provide energy substrates to axons predominantly by delivery of glucose, indicating different metabolic support mechanisms among white matter regions.