Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing

Abstract

Neural activity has been suggested to initially trigger ATP production by glycolysis, rather than oxidative phosphorylation, for three reasons: glycolytic enzymes are associated with ion pumps; neurons may increase their energy supply by activating glycolysis in astrocytes to generate lactate; and activity increases glucose uptake more than O 2 uptake. In rat hippocampal slices, neuronal activity rapidly decreased the levels of extracellular O 2 and intracellularNADH(reduced nicotinamide adenine dinucleotide), even with lactate dehydrogenase blocked to prevent lactate generation, or with only 20% superfused O 2 to mimic physiological O 2 levels. Pharmacological analysis revealed an energy budget in which 11% of O 2 use was on presynaptic action potentials, 17% was on presynaptic Ca 2+ entry and transmitter release,46%was on postsynaptic glutamate receptors, and26%was on postsynaptic action potentials, in approximate accord with theoretical brain energy budgets. Thus, the major mechanisms mediating brain information processing are all initially powered by oxidative phosphorylation, and an astrocyte-neuron lactate shuttle is not needed for this to occur. © 2012 the authors.