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

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 permeabil ity. The regional and cellular distribution of calcium-permeable kainate/AM PA receptors has not been extensively investigated, however. In this study, we used a histochemical technique, the kainate-stimulated cobalt uptake as say, 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 concent ration-dependent (1 mu M-1 mM) and was blocked by the glutamate receptor an tagonist, kynurenate. The specific cellular location of cobalt labeling var ied regionally within the hippocampal formation, switching from selective l abeling of only apical dendrites in Ammon's horn subregion 1a (CA1a) to a d iffuse band of punctate labeling in CA1c to labeling of cell bodies along w ith their proximal dendrites in CA3. Furthermore, increasing the kainate co ncentration not only enhanced the intensity of cobalt labeling, but also ch anged the pattern of cellular staining from exclusively dendritic labeling to extensive staining of both cell bodies and dendrites in CA1a pyramidal n eurons. High kainate concentrations or prolonged incubation times produced a diffuse cellular labeling suggestive of neurotoxicity. These data are con sistent with evidence that specific kainate and AMPA receptor subunit combi nations are targeted to specific synapses in hippocampal pyramidal neurons. J. Comp. Neurol. 402:141-154, 1998. (C) 1998 Wiley-Liss, Inc.