Excitatory amino acid receptors in the human cerebral cortex: A quantitative autoradiographic study comparing the distributions of [ 3H]TCP, [ 3H]glycine, l-[ 3H]glutamate, [ 3H]AMPA and [ 3H]kainic acid binding sites

Abstract

The excitatory amino acids are probably the major neurotransmitters in the cerebral cortex, and they act through at least three receptors: the N-methyl- d-aspartate , the quisqualate and the kainic acid receptors. Under the appropriate conditions, [ 3H]1-(1-(2-thienyl)-cyclohexyl)piperidine ([ 3H]TCP), [ 3H]glycine and l-[ 3H]glutamate label different sites on the N-methyl- d-aspartate receptor , [ 3H]-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ([ 3H]AMPA) labels the quisqualate receptor and [ 3H]kainic acid the kainic acid receptor. The anatomical localizations of these binding sites were studied in sections of blocks removed from the cerebral cortices of eight post-mortem human brains. The results showed that, in the human cerebral cortex, [ 3H]TCP, [ 3H]glycine and l-[ 3H]glutamate binding sites had congruent distributions, with [ 3H]AMPA binding sites showing a similar distribution. In the hippocampus, these four ligands had high binding site densities in the CA1 region and the dentate gyrus molecular layer. With the exception of the striate cortex, in the neocortex, a tri-laminar pattern was seen consisting of a high density across laminae I–III, a layer of low density corresponding to the region of lamina IV, and a band of moderate density across laminae V and VI, except for [ 3H]AMPA where the middle zone of low density was usually wider. [ 3H]Kainic acid showed a binding pattern which was generally complementary to that of the other four ligands. There were very low levels of [ 3H]kainic acid binding sites in the CA1 region of the hippocampus with higher levels in the CA3 region, the hilus, and the inner third of the dentate gyrus molecular layer. In the neocortex there was a band of high density corresponding to laminae V and VI, with a thin band of moderate binding corresponding to lamina I and the outer region of lamina II. An exception was the motor cortex where the highest level of [ 3H]kainic acid binding was in laminae I and II. The high degree of congruence between the binding patterns of [ 3H]TCP, [ 3H]glycine and l[ 3H]glutamate (using conditions appropriate for the N-methyl- d-aspartate receptor) supports data indicating that these ligands bind to different regions of the same receptor complex. The similar distribution of [ 3H]AMPA binding sites, with the exception of the striate cortex, supports observations made in rodents that N-methyl- d-aspartate receptors and quisqualate receptors have similar distributions and perform different but related functions in excitatory transmission. The complementary distribution of kainic acid receptors supports the proposal that excitatory amino acid neurotransmission may involve several anatomically separate systems. The pattern in the primary motor cortex is consistent with evidence from studies of other receptors suggesting a unique chemoarchitecture for this region.