Anatomical organization of excitatory amino acid receptors and their pathways

Abstract Synapses that employ excitatory amino acids (EAA) as their neurotransmitter use multiple combinations of receptors, apparently yielding different functional properties. The most well-characterized receptor class, the N-methyl-d-aspartate (NMDA) receptor, is found throughout the brain but primarily in telencephalic regions. Phencyclidine and glycine binding sites, which interact allosterically with NMDA receptors, have almost identical distributions. NMDA sites also extensively overlap with the quisqualate excitatory amino acid receptor class, but are less often found co-localized with the kainate receptor class. Evidence obtained with presynaptic markers - high affinity glutamate or aspartate uptake, Ca 2+ -dependent release, and glutamate and aspartate contents - each indicate that EAA are major transmitters of corticocortical, corticofugal, and sensory systems. Recent advances in the histological analysis of these markers are now providing a more detailed map of the excitatory amino acid system and this anatomical map appears to correspond to the distribution of the sum of the receptors. Thus the receptor systems may represent distinct, anatomically-organized, subsystems of excitatory amino acid-mediated neurotransmission.