A COMPLEX MOSAIC OF HIGH-AFFINITY KAINATE RECEPTORS IN RAT-BRAIN

The significance for CNS function of glutamate-gated cation channels t hat exhibit high-affinity kainate sites is not understood. Such recept ors, which on dorsal root ganglia and in recombinant systems exhibit c urrents that rapidly desensitize to kainate application, have not been detected electrophysiologically in the brain. However, a comparison o f the distribution of mRNAs encoding five glutamate receptor subunits exhibiting high-affinity kainate sites (GluR-5-GluR-7, KA-1, and KA-2) indicates that high-affinity kainate receptors are most likely involv ed in all central neuronal circuits of the rat brain. The KA-1 mRNA oc curs mainly in the CA3 field of the hippocampus and dentate gyrus, wit h much lower amounts being found in inner cortical layers, cerebellar Purkinje cells, and white matter (e.g., corpus callosum and anterior c ommissure). The KA-2 gene is widely expressed in many neuronal nuclei including layers II-VI of neocortex, hippocampal pyramidal (CA1-CA3) a nd dentate granule cells, septal nuclei such as the bed nucleus of the stria terminalis, medial preoptic, suprachiasmatic, and ventral media l hypothalamic nuclei, dorsal raphe, locus coeruleus, and cerebellar g ranule cells. KA-2 mRNA is also found in the pineal gland. GluR-5 tran scripts are in the cingulate and piriform cortex, the subiculum, later al septal nuclei, anteroventral thalamus, suprachiasmatic nucleus, the tegmental nuclei, pontine nuclei, and Purkinje cells. GluR-6 mRNA is most abundant in cerebellar granule cells, with lower levels in caudat e-putamen and the pyramidal cell layers and dentate granule cells of h ippocampus. The GluR-7 gene is prominently expressed in the inner neoc ortical layers and some cells in layer II, subiculum, caudate-putamen, reticular thalamus, ventral medial hypothalamic nucleus, pontine nucl ei, and in putative stellate/basket cells in the cerebellum. These fin dings suggest that a complex mosaic of receptor variants underlies the high-affinity kainate receptor in the vertebrate brain.