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 (1). About ten year ago we provided experimental evidence indicating a central role of astrocytes in neurometabolic coupling (2). 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 (3). Analyses of this coupling have been extended in vivo (4,5), 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 syncytium (6,7).On the basis of a large body of experimental evidence (for a recent review see 8,9) we have proposed an operational model, "the astrocyte-neuron lactate shuttle" (10,11). Recently a series of results obtained by independent laboratories has provided further support for this model (12-14). 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, distinct subregions of the hippocampus are metabolically active at different time-points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron- glia coupling, occurs during learning (Ros et al., in press). In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for Protein targeting to Glycogen (PTG) following sleep-deprivation (15). These data suggest that glial metabolic plasticity is likely to be a concomitant of synaptic plasticity.