1. ¹Department of Diagnostic Radiology, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA
2. ²Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA

Correspondence: Dr GMI Chowdhury, Magnetic Resonance Research Center, Department of Diagnostic Radiology, Yale University School of Medicine, TAC-MRRC, N150, PO Box 208043, New Haven, Connecticut 06520, USA. E-mail: golam.chowdhury@yale.edu; Dr KL Behar, Magnetic Resonance Research Center, Department of Psychiatry, Yale University School of Medicine, TAC-MRRC, N150, PO Box 208043, New Haven, Connecticut 06520, USA. E-mail: kevin.behar@yale.edu

³Current address: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007 India.

Received 27 September 2006; Revised 19 January 2007; Accepted 25 February 2007; Published online 18 April 2007.

Abstract

The contribution of glutamatergic and -aminobutyric acid (GABA)ergic neurons to oxidative energy metabolism and neurotransmission in the developing brain is not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused intravenously with [1,6-¹³C₂]glucose for different time intervals (time course) or with [2-¹³C]acetate for 2 to 3 h (steady state). Amino acid levels and ¹³C enrichments were determined in tissue extracts ex vivo using ¹H-[¹³C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and astroglia) to the ¹³C-enrichment time courses of amino acids from [1,6-¹³C₂]glucose, constrained by the ratios of neurotransmitter cycling (V_cyc)-to-tricarboxylic acid (TCA) cycle flux (V_TCAn) calculated from the steady-state [2-¹³C]acetate enrichment data. From P10 to P30 increases in total neuronal (glutamate plus GABA) TCA cycle flux (3 ; 0.240.05 versus 0.710.07 mol per g per min, P<0.0001) and total neurotransmitter cycling flux (3.1 to 5 ; 0.07 to 0.11 (0.03) versus 0.340.03 mol per g per min, P<0.0001) were approximately proportional. Incremental changes in total cycling (V_cyc(tot)) and neuronal TCA cycle flux (V_TCAn(tot)) between P10 and P30 were 0.23 to 0.27 and 0.47 mol per g per min, respectively, similar to the 1:2 relationship previously reported for adult cortex. For the individual neurons, increases in V_TCAn and V_cyc were similar in magnitude (glutamatergic neurons, 2.7 versus 2.8 to 4.6 ; GABAergic neurons, 5 versus 7 ), although GABAergic flux changes were larger. The findings show that glutamate and GABA neurons undergo large and approximately proportional increases in neurotransmitter cycling and oxidative energy metabolism during this major postnatal growth spurt.