Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-13C]GABA derived from glia-specific substrate [2-13C]acetate

Brain [2-13C]γ-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-13C]acetate reflects the extent of the GABA–glutamine neurotransmitter cycling between GABAergic neurons and glial cells. We report, for the first time, in vivo quantification of the GABA–glutamine cycling flux. The GABA–glutamine cycling flux rate was determined to be 1.8 ± 0.4 μmol/(g h) (mean ± S.D., n = 6, ∼6% of total tricarboxylic acid cycle rate) in the neocortex of vigabatrin-treated rats. The relatively small magnitude of glial contribution to the clearance of extracellular GABA measured in this study provided in vivo evidence to support the concept of a significant neuronal reuptake of GABA, which short-circuits the GABA–glutamine cycling pathway for repletion of released neurotransmitter GABA.