The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function which has provided the basis for 2-deoxyglucose-based functional imaging with PET. Fifteen years ago, we provided experimental evidence indicating a central role of astrocytes in neurometabolic coupling. The basic mechanism in neurometabolic coupling is the glutamate-stimulated aerobic glycolysis in astrocytes, such that the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and its glycolytic processing, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. Analyses of this coupling have been extended in vivo, and recently have also defined the modalities of coupling for inhibitory neurotransmission as well as its spatial extent in relation to the propagation of metabolic signals within the astrocytic syncitium. On the basis of a large body of experimental evidence, we have proposed an operational model “the astrocyte-neuron lacatte shuttle”. A series of results obtained by independent laboratories has provided further support for this model (For review see Pellerin et al). This body of evidence provides a molecular and cellular basis for interpreting data obtained with functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel to adaptive mechanisms that characterize synaptic plasticity. Thus, specific genes involved in neurometabolic coupling are modulated in the hippocampus during spatial learning and inhibitory avoidance tasks. A proinflammatory environment as well as the pathogenic form of beta-amyloid (1-42) modifies the metabolic phenotype of astrocytes, affecting neuronal survival (Allaman et al). In addition, marked variations in the expression of genes in glial glucose and glycogen metabolism are observed during the sleep-wake cycle (Petit et al). Altogether these data suggest that glial metabolic plasticity is likely to be a concomitant of synaptic plasticity.