Astrocytes: Glutamate producers for neurons

In order for the brain to use the common amino acid glutamate as a neurotra nsmitter, it has been necessary to introduce a series of innovations that g reatly restrict the availability of glutamate, so that it cannot degrade th e signal-to-noise ratio of glutamatergic neurons. The most far-reaching inn ovations have been: i) to exclude the brain from access to glutamate in the systemic circulation by the blood-brain barrier, thereby making the brain autonomous in the production and disposal of glutamate; ii) to surround glu tamatergic synapses with glial cells and endow these cells with much more p owerful glutamate uptake carriers than the neurons themselves, so that most released transmitter glutamate is rapidly inactivated by uptake in glial c ells; iii) to restrict to glial cells a key enzyme (glutamine synthetase) t hat is involved in the return of accumulated glutamate to neurons by amidat ion to glutamine, which has no transmitter activity, and can be safely rele ased to the extracellular space, returned to neurons and deaminated to glut amate; iv) to restrict to glial cells two key enzymes (pyruvate carboxylase and cytosolic malic enzyme) that are involved in, respectively, de novo sy nthesis (from glucose) of the carbon skeleton of glutamate, and the return of the carbon skeleton of excess glutamate to the metabolic pathway for glu cose oxidation, As a consequence of these innovations, neurons constantly r equire new carbon skeletons from glial to sustain their TCA cycle. When the se supplies are withdrawn, neurons are unable to generate amino acid transm itters and their rate of oxidative metabolism is impaired. Given the commen salism that exists between neurons and glia, it may be fruitful to view bra in function not just as a series of interactions between neurons, but also as a series of interactions between neurons and their collaborating glial c ells. (C) 1999 Wiley-Liss, Inc.