Regulation of Neuron-Astrocyte Metabolic Coupling across the Sleep-Wake Cycle

Over the last thirty years, a growing number of studies showed that astrocytes play a pivotal role in the energy support to synapses. More precisely, astrocytes adjust the energy production to the neuronal energy needs through different mechanisms grouped under the term “neurometabolic coupling” (NMC). In this review we describe these mechanisms of coupling and how they involve astrocytes. From a physiological point of view, these mechanisms of coupling are particularly important to ensure normal synaptic functioning when neurons undergo rapid and repetitive changes in firing rate such as during the sleep/wake transitions. Investigations on brain energy metabolism during the sleep/wake cycle have been mainly focused on glucose consumption and on glycogen metabolism. However, the recent development of substrate-specific biosensors allowed measurements of the variation in extracellular levels of glutamate, glucose and lactate with a time resolution compatible with sleep stage duration. Together with gene expression data these experiments allowed to better define the variations of energy metabolites regulation across the sleep/wake cycle. The aim of this review is to bring into perspective the role of astrocytes and neurometabolic coupling in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the “local and use dependent” sleep hypothesis.