In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics

In this article we review recent studies, primarily from our laboratory, us ing C-13 NMR (nuclear magnetic resonance) to non-invasively measure the rat e of the glutamate-glutamine neurotransmitter cycle in the cortex of rats a nd humans. In the glutamate-glutamine cycle, glutamate released from nerve terminals is taken up by surrounding glial cells and returned to the nerve terminals as glutamine. C-13 NMR studies have shown that the rate of the gl utamate-glutamine cycle is extremely high in both the rat and human cortex, and that it increases with brain activity in an approximately 1:1 molar ra tio with oxidative glucose metabolism. The measured ratio, in combination w ith proposals based on isolated cell studies by P.J. Magistretti and co-wor kers, has led to the development of a model in which the majority of brain glucose oxidation is mechanistically coupled to the glutamate-glutamine cyc le. This model provides the first testable mechanistic relationship between cortical glucose metabolism and a specific neuronal activity. We review he re the experimental evidence for this model as well as implications for blo od oxygenation level dependent magnetic resonance imaging and positron emis sion tomography functional imaging studies of brain function.