Neurons and Glia Talk Amongst Themselves

Abstract

Voutsinos-Porche et al. used mutant mice lacking glial glutamate transporters to study the effects of synaptic activity on glucose utilization by astrocytes and discovered evidence for metabolic crosstalk between neurons and astrocytes through a mechanism involving glial glutamate uptake and the ensuing changes in glial intracellular Na + concentration [Na + ] i . Astrocytes have long been suspected of contributing to the metabolic support of neurons, but there has been little direct evidence. Mutant mice lacking one or the other of the glial glutamate transporters GLAST or GLT-1 showed reduced 2-deoxyglucose (2-DG) accumulation (a measure of glycolytic activity) in somatosensory cortex after whisker stimulation. In primary cultures, cortical astrocytes from GLAST − mice showed reduced uptake of the nonmetabolized glutamate analog aspartate, as well as reduced stimulation of 2-DG uptake and of lactate release after exposure to glutamate. A glutamate-dependent increase in [Na + ] i secondary to Na + cotransport with glutamate was also attenuated. The increase in 2-DG uptake and lactate release in response to glutamate were restored by pharmacological manipulation with cyclothiazide to stimulate glutamate-dependent Na + influx through the L-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor. The effect of cyclothiazide was abolished in medium in which lithium, which cannot replace Na + on the Na + ,K + -ATPase, was substituted for Na + . The authors proposed a model in which activation of glial Na + ,K + -ATPase by increased [Na + ] i promotes enhanced glycolysis and lactate output. The lactate is then available as an additional energy source for the firing neurons that released the glutamate. B. Voutsinos-Porche, G. Bonvento, K. Tanaka, P. Steiner, E. Walker, J.-Y. Chatton, P. J. Magistretti, L. Pellerin, Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37 , 275-286 (2003). [Online Journal]