Regional and laminar specificity of kainate-stimulated cobalt uptake in the rat hippocampal formation

Abstract

Kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were initially found to be impermeable to calcium, but cloning and expression studies subsequently revealed that certain kainate and AMPA receptor subunit combinations display substantial divalent cation permeability. The regional and cellular distribution of calcium-permeable kainate/AMPA receptors has not been extensively investigated, however. In this study, we used a histochemical technique, the kainate-stimulated cobalt uptake assay, to localize calcium-permeable kainate responsive receptors in the rat hippocampal formation. In the presence of cobalt, kainate produced a highly localized, dark granular precipitate in dendrites, perikarya, or both, of hippocampal neurons. Kainate-stimulated cobalt uptake was time- and concentration-dependent (1 microM-1 mM) and was blocked by the glutamate receptor antagonist, kynurenate. The specific cellular location of cobalt labeling varied regionally within the hippocampal formation, switching from selective labeling of only apical dendrites in Ammon's horn subregion la (CA1a) to a diffuse band of punctate labeling in CA1c to labeling of cell bodies along with their proximal dendrites in CA3. Furthermore, increasing the kainate concentration not only enhanced the intensity of cobalt labeling, but also changed the pattern of cellular staining from exclusively dendritic labeling to extensive staining of both cell bodies and dendrites in CA1a pyramidal neurons. High kainate concentrations or prolonged incubation times produced a diffuse cellular labeling suggestive of neurotoxicity. These data are consistent with evidence that specific kainate and AMPA receptor subunit combinations are targeted to specific synapses in hippocampal pyramidal neurons.