The idea of a metabolic coupling between neurons and astrocytes in the brain has been entertained for about 100 years. The use recently of simple and well-compartmentalized nervous systems, such as the honeybee retina or purified preparations of neurons and glia, provided strong support for a nutritive function of glial cells: glial cells transform glucose to a fuel substrate taken up and used by neurons. Particularly, in the honeybee retina, photoreceptor-neurons consume alanine supplied by glial cells and exogenous proline. NH4+ and glutamate are transported into glia by functional plasma membrane transport systems. During increased activity a transient rise in the intraglial concentration of NH4+ or of glutamate causes a net increase in the level of reduced nicotinamide adenine dinucleotides [NAD(P)H]. Quantitative biochemistry showed that this is due to activation of glycolysis in glial cells by the direct action of NH4+ and of glutamate, probably on the enzymatic reactions controlled by phosphofructokinase alanine aminotransferase and glutamate dehydrogenase. This activation leads to a massive increase in the production and release of alanine by glia. This constitutes an intracellular signal and it depends upon the rate of conversion of NH4+ and of glutamate to alanine and alpha-ketoglutarate, respectively, in the glial cells. Alanine and alpha-ketoglutarate are released extracellularly and then taken up by neurons where they contribute to the maintenance of the mitochondrial redox potential. This signaling raises the novel hypothesis of a tight regulation of the nutritive function of glia.