Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-13C6]glucose

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying (18)FDG-PET and indirect C-13 magnetic resonance spectroscopy (H-1-[C-13]-MRS) at 14.1 T upon infusion of uniformly C-13-labeled glucose ([U-C-13(6)]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-C-13(6)]Glc and refining the compartmentalized model by including two gamma-aminobutyric acid (GABA) pools permit us to evaluate the relative contributions of glutamatergic and GABAergic metabolism to total hippocampal neuroenergetics. We report that GABAergic activity accounts for similar to 13% of total neurotransmission (V-NT) and similar to 27% of total neuronal TCA cycle (V-TCA) in mouse hippocampus suggesting a higher V-TCA/V-NT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of C-13-MRS in specific brain regions of small animals.