The energetics of CNS white matter

The energetics of CNS white matter are poorly understood. We derive a signaling energy budget for the white matter (based on data from the rodent optic nerve and corpus callosum) which can be compared with previous energy budgets for the gray matter regions of the brain, perform a cost-benefit analysis of the energetics of myelination, and assess mechanisms for energy production and glucose supply in myelinated axons. We show that white matter synapses consume ≤0.5% of the energy of gray matter synapses and that this, rather than more energy-efficient action potentials, is the main reason why CNS white matter uses less energy than gray matter. Surprisingly, while the energetic cost of building myelin could be repaid within months by the reduced ATP cost of neuronal action potentials, the energetic cost of maintaining the oligodendrocyte resting potential usually outweighs the saving on action potentials. Thus, although it dramatically speeds action potential propagation, myelination need not save energy. Finally, we show that mitochondria in optic nerve axons could sustain measured firing rates with a plausible density of glucose transporters in the nodal membrane, without the need for energy transfer from oligodendrocytes.