EXCITATORY AMINO-ACID TRANSMITTERS AND THEIR RECEPTORS IN NEURAL CIRCUITS OF THE CEREBRAL NEOCORTEX

In 1954, l-glutamate (Glu) and l-aspartate (Asp) were first suggested as being excitatory synaptic transmitters in the cerebral cortex. Since then, evidence has mounted steadily in favor of the view that Glu and Asp are major excitatory transmitters in the neocortex. Many of the experimental studies which reported how Glu/Asp came to satisfy the criteria for transmitters in the neocortex are reviewed here, according to the methods employed. Since the question of which particular synaptic sites in cortical neural circuits Glu/Asp operate as excitatory transmitters has not previously been reviewed, particular attention is given to efferent, afferent and intrinsic neural circuits of the visual and somatosensory cortices, where circuitry is relatively clearly delineated. Recent studies using chemical assays of released amino acids, high-affinity uptake mechanisms of Glu/Asp from nerve terminals, the direct micro-iontophoretic administration of Glu/Asp antagonists, and immunocytochemical techniques have demonstrated that almost all corticofugal efferent projections employ Glu/Asp as excitatory synaptic transmitters. Evidence indicating that thalamocortical afferent projections, including geniculocortical projections and some intrinsic connections are glutamatergic, is also reviewed. Thus, the results highlighted here indicate that the main framework of neocortical circuitry is operated by Glu/Asp. Pharmacological studies indicate that synaptic receptors for Glu/Asp can be classified into a few subtypes, including N-methyl-d-aspartate (NMDA) and quisqualate/kainate (non-NMDA) types. Some evidence indicating the sites of operation of NMDA and non-NMDA receptors in neocortical circuitry is reviewed, and the distinct, functional significance of these two types of Glu/Asp receptors in information processing in the neocortex is proposed. © 1990.