Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus
upon infusion of [U-13C6]glucose |
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Authors: | Antoine Cherix Guillaume Donati Blanca Lizarbe Bernard Lanz Carole Poitry-Yamate Hongxia Lei Rolf Gruetter |
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Affiliation: | 1.Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;2.Instituto de Investigaciones Biomedicas “Alberto Sols”, CSIC-UAM, Madrid, Spain;3.Sir Peter Mansfield Imaging Centre (SPMIC), School of Medicine, University of Nottingham, Nottingham, UK;4.Center for Biomedical Imaging (CIBM-AIT), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland |
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Abstract: | 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 18FDG-PET and indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) at 14.1 T upon infusion of uniformly 13C-labeled glucose ([U-13C6]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-13C6]Glc and refining the compartmentalized model by including two γ-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 ∼13% of total neurotransmission (VNT) and ∼27% of total neuronal TCA cycle (VTCA) in mouse hippocampus suggesting a higher VTCA/VNT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of 13C-MRS in specific brain regions of small animals. |
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Keywords: | 1H-[13C]-MRS neuronal metabolism metabolic modeling TCA cycle mouse hippocampus |
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