AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBTYPE IMMUNOREACTIVITY IN THE AGED HUMAN HIPPOCAMPAL-FORMATION

It has been hypothesized that, in Alzheimer's disease, glutamate-media ted excitotoxicity contributes to the degeneration of selected populat ions of neurons. In the present study, immunocytochemical techniques w ere used to determine the distribution and anatomical features of GluR 1- and GluR2/3-immunolabeled cell bodies and processes within the hipp ocampal formation of normal (i.e., no pathology) elderly humans. The r esults of this study provide an essential baseline with which to compa re the expression and distribution of glutamate receptor subunits with in the brains of patients with Alzheimer's disease. With respect to Gl uR1 immunoreactivity, the molecular layer of the dentate gyrus display s the most intense immunolabeling of any hippocampal structure. Contri buting to this intense labeling are apical dendrites that arise from n eurons within the adjacent granule cell layer. Interestingly, GluR1-la beled neurons account for a relatively small percentage of the total n umber of neurons as revealed by Nissl staining in the granule cell lay er. In contrast, GluR2/3-labeled neurons are densely distributed throu ghout the granule cell layer, yet they provide relatively few processe s to the adjacent molecular layer compared to GluR1-positive processes . GluR1 labeling is also prominent within the CA fields of Ammon's hor n, with CA2 > CA3 > CA1 greater than or equal to CA4. Most prominent w ithin the CA fields are the labeled dendrites of pyramidal neurons. In many instances, apical dendrites can be traced into the adjacent stra tum radiatum, where they impart a deep striated appearance to this reg ion of the hippocampus. Robust GluR2/3 labeling is also observed withi n the pyramidal layer of Ammon's horn, with an order of staining inten sity similar to that observed for GluR1. However, unlike GluR1 labelin g, which is localized predominantly along dendrites, GluR2/3 labeling is observed primarily in association with cell bodies. Collectively, t hese data suggest that the molecular composition of the AMPA receptor complex may differ between the dendrite and soma of granule and pyrami dal neurons within the hippocampal formation, so functionally we may p redict that these two regions of the neuron would respond differently following glutamate receptor stimulation. (C) 1995 Wiley-Liss, Inc.