Energetic costs associated with glutamatergic and gabaergic neurotransmission

Previous studies have shown that the glutamate/glutamine neurotransmitter cycle and neuronal glucose oxidation are proportional (1:1) with increasing neuronal activity above isoelectricity. γ-Aminobutyric acid (GABA), a product of glutamate metabolism, is synthesized from astroglial glutamine and contributes to total ‘glutamate/glutamine’ neurotransmitter cycling, although the fraction contributed by GABA is unknown. In the present study we used 13C NMR spectroscopy together with intravenous infusions of [1,6-13C2]glucose, and [2-13C]acetate to separately determine rates of glutamate/glutamine and GABA/glutamine cycling and their respective TCA cycles in the rat cortex under conditions of halothane anesthesia and pentobarbital-induced isoelectricity. Under 1% halothane anesthesia GABA/glutamine cycle flux comprised 23% of total (glutamate + GABA) neurotransmitter cycling and 18% of total neuronal TCA cycle flux. In isoelectric cortex glucose oxidation was reduced >3-fold in glutamatergic and GABAergic neurons and neurotransmitter cycling was below detection. Hence, in both cell types the primary energetic costs are associated with neurotransmission, which increase together as cortical activity is increased. The contribution of GABAergic neurons and inhibition to cortical energy metabolism has broad implications for the interpretation of functional imaging signals.