Role of astrocytes in coupling synaptic activity to glucose utilization

Recently, in vitro evidence has suggested that astrocytes might play an important role in coupling neuronal activity to glucose utilization. The mechanism proposed to explain such coupling involves the uptake of glutamate by astrocytes via specific transporters. Here, we have taken advantage of the existence of knockout (KO) mice for each glial glutamate transporter to further explore the underpinnings of this mechanism, both in vitro and in vivo. Experiments performed on cultured cortical astrocytes from these mice indicate that an increase in intracellular Na⁺ concentration caused by glutamate transport via the glutamate transporter GLAST is necessary to induce an increase in glucose utilization and lactate production. In vivo, the role of glial glutamate transporters in coupling neuronal activity to energy metabolism was further explored using the whisker-to-barrel pathway. Specific stimulation of the whiskers caused an accumulation of ¹⁴C-2-deoxyglucose in related areas of the somatosensory cortex in wild type mice at the age of postnatal day 10. In both GLAST and GLT-1 transporter knockout mice, the metabolic response was strongly reduced. These data further emphasized the prominent role of astrocytes in the regulation of brain energy metabolism and identify glial glutamate transporters as key elements.