Figure 2.

Proposed concept derived from the astrocyte–neuron lactate shuttle (ANLS) model that brain imaging signals based on glucose uptake primarily reflect astrocyte metabolism. During synaptic activity, glutamate is released into the synaptic cleft. A glutamate transporter system on astrocytes ensures removal of glutamate from the synaptic cleft. The entry of Na⁺ cotransported with glutamate activates the Na⁺/K⁺ ATPase. Activation of the Na⁺/K⁺ ATPase is coupled with an increased glycolytic flux, hence resulting in the stimulation of glucose uptake from the capillaries. Lactate, the major end product of glycolysis, is released by astrocytes and taken up by neurons where it can enter the tricarboxylic acid (TCA) cycle and provide 18 ATP per molecule. This model implies that the activity-linked uptake of ¹⁸Fluorodeoxyglucose (¹⁸FDG) monitored with positron emission tomography (PET) reflects primarily an astrocyte-based signal. However, since neuronally released glutamate triggers the cascade of events that leads to glucose uptake, the ¹⁸FDG-PET signal faithfully reflects activation of neuronal circuits. Taken from Magistretti and Pellerin (1996). fMRI, functional magnetic resonance imaging.