Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo

The regulation of brain energy metabolism during neuronal activation is poo rly understood. Specifically, the extent to which oxidative metabolism rath er than glycolysis supplies the additional ATP necessary to sustain neurona l activation is in doubt. A recent hypothesis claims that astrocytes genera te lactate with the muscle-type lactate dehydrogenase (LDH) isozyme LD5. La ctate from astrocytes then undergoes oxidation in neurons after reconversio n to pyruvate by the LDH subtype LD1. On the basis of this hypothesis, the authors predicted that the time course of an excitatory increase of the oxi dative metabolism of brain tissue must depend on the degree to which astroc ytes provide neurons with pyruvate in the form of lactate. From the known p roperties of the LDH subtypes, the authors predicted two time courses for t he changes of oxygen consumption in response to neuronal stimulation: one r eflecting the properties of the neuronal LDH subtype LD1, and the other ref lecting the astrocytic LDH subtype LD5. Measuring oxygen consumption (CMRo( 2)) with positron emission tomography, the authors demonstrated increased C MRo(2) during sustained stimulation of visual cortex with a complex stimulu s. The CMRo(2) increased 20.5% after 3 minutes and 27.5% after 8 minutes of stimulation, consistent with a steady-state oxygen-glucose metabolism rati o of 5.3, which is closest to the index predicted for the LD1 subtype. The index is equal to the oxygen-glucose metabolism ratio of 5.5 calculated at baseline, indicating that pyruvate is converted to lactate in a cellular co mpartment with an LDH reaction closest to that of LD1, whether at rest or d uring stimulation of the visual cortex with the current stimulus. The findi ngs are consistent with a claim that neurons increase their oxidative metab olism in parallel with an increase of pyruvate, the latter generated by neu ronal rather than astrocytic glycolysis.