Cellular mechanisms of brain energy metabolism: implications for functional brain imaging

Signals detected with functional brain imaging techniques are based on the coupling of neuronal activity with energy metabolism. Techniques such as po sitron emission tomography (PET) and functional magnetic resonance imaging (fMRI) allow the visualization of brain areas that are activated by a varie ty of sensory, motor or cognitive tasks. Despite the technological sophisti cation of these brain imaging techniques, the precise mechanisms and cell t ypes involved in coupling and in generating metabolic signals are still deb ated. Recent experimental data on the cellular and molecular mechanisms tha t underlie the fluorodeoxyglucose (FDG) - based PET imaging point to a crit ical role of a particular brain cell type, the astrocytes, in coupling neur onal activity to glucose utilization. Indeed, astrocytes possess receptors and re-uptake sites for a variety of neurotransmitters, including glutamate , the predominant excitatory neurotransmitter in the brain, In addition, as trocytic end-feet, which surround capillaries, are enriched in the specific glucose transporter GLUT-1. These features allow astrocytes to "sense" syn aptic activity and to couple it with energy metabolism. In vivo and in vitr o data support the following functional model: in response to glutamate rel eased by active neurons, glucose is predominantly taken up by astrocytic en d-feet; glucose is then metabolized to lactate which provides a preferred e nergy substrate for neurons. These data support the notion that astrocytes markedly contribute to the FDG-PET signal.