SELECTIVE DISTRIBUTION OF KAINATE RECEPTOR SUBUNIT IMMUNOREACTIVITY IN MONKEY NEOCORTEX REVEALED BY A MONOCLONAL-ANTIBODY THAT RECOGNIZES GLUTAMATE-RECEPTOR SUBUNITS GLUR5 6/7/

A monoclonal antibody (4F5) was generated against a portion of the put ative extracellular domain of glutamate receptor subunit GluR5. Wester n blot analyses and immunocytochemistry of transfected human embryonic kidney 293 cells confirmed that monoclonal antibody 4F5 was specific for GluR5, -6, and -7 (the three identified members of the kainate rec eptor subunit class), but did not recognize GluR1, -2, or -3 (the AMPA /kainate receptor subunit class). The antibody was subsequently used t o examine immunocytochemically the regional, laminar, and cellular dis tribution of GluR5/6/7 receptor subunits at the light and electron mic roscopic levels in monkey neocortex. Receptor subunit immunoreactivity was present throughout all cortical areas examined, but exhibited mar ked cellular, laminar, and regional specificity. Typically, pyramidal cell somata and apical dendrites were well stained. Electron microscop y revealed an extensive cytoplasmic localization of GluR5/6/7 immunopr ecipitate, with intense staining of many postsynaptic densities, all o f which were associated with asymmetric synapses located on dendritic shafts or dendritic spines. There was no evidence of stained glial cel ls or presynaptic axon terminals. In most areas, labeled cells and den drites were concentrated in layers II, III, and V while layers I, IV, and VI typically possessed the fewest and/or least intensely stained e lements. A consistent feature in many areas was groups of clustered la yer V pyramidal cells and bundles of ascending apical dendrites. Regio nally, motor areas and higher-order association areas of the frontal, parietal, and occipital lobes were more densely stained than primary s ensory areas (somatic sensory and visual cortex), which was confirmed quantitatively. These data indicate a high degree of selectivity in th e distribution of kainate receptors composed of GluR5/6/7 subunits, an d suggest that functional specificity and diversity in the ubiquitous excitatory amino acid-utilizing axonal systems in neocortex are achiev ed in part by the differential association of particular glutamate rec eptor subunits with specific cortical circuits. In addition, the regio nal, laminar, and morphological characteristics of GluR5/6/7-immunorea ctive neurons bear a strong similarity to those of the neocortical neu rons with heightened vulnerability in certain neurodegenerative disord ers.