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Journal of Neuroscience, Vol 15, 2707-2719, Copyright © 1995 by Society for Neuroscience
Distribution of the excitatory amino acid receptor subunits GluR2(4) in monkey hippocampus and colocalization with subunits GluR5-7 and NMDAR1
SJ Siegel, WG Janssen, JW Tullai, SW Rogers, T Moran, SF Heinemann and JH Morrison
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Ionotropic excitatory amino acid (EAA) receptors are divided
pharmacologically into three categories termed NMDA, AMPA/kainate, and high
affinity kainate receptors. Each of these receptor subtypes is composed of
a specific subset of subunits termed GluR1-4 (AMPA/kainate), GluR5-7, KA1-2
(high affinity kainate), and NMDAR1, 2 A- D (NMDA). Although colocalization
of NMDA and non-NMDA receptors has been previously demonstrated
electrophysiologically in rat, comprehensive analyses of subunit specific
colocalization patterns have not been possible until the advent of
appropriate antibodies. The present study investigates such
immunocytochemical colocalization of several EAA receptor subunits within
individual cells as well as dendritic spines in the monkey hippocampus.
Double-label immunohistochemical experiments using antibodies which are
specific for GluR2(4), GluR5-7, and NMDAR1 demonstrated that virtually all
projection neurons in each subfield of the hippocampus contain subunits
from the AMPA/kainate, kainate, and NMDA receptor families. In addition,
confocal microscopy has demonstrated that individual spines may contain
subunits representative of multiple EAA receptor families. Furthermore,
detailed regional, cellular, and ultrastructural distribution patterns of
the EAA receptor subunits GluR2 and GluR4 in monkey hippocampus are
presented based on the use of a monoclonal antibody (mAb), 3A11, which was
generated against the putative extracellular N-terminal domain of GluR2.
Since this antibody recognizes only GluR2 in Western blots, and GluR2 as
well as GluR4 in fixed transiently transfected cells, it has been
designated anti- GluR2(4). Immunocytochemical labeling with mAb 3A11
revealed pyramidal cell somata and dendrites in each field of the
hippocampus, as well as granule cells and polymorphic hilar cells in the
dentate gyrus. Small cells with the morphologic characteristics of
astroglia were also immunolabeled for GluR2(4) within the alveus and
fimbria. Immunoreactivity at the ultrastructural level was localized to
postsynaptic densities on dendritic spines and shafts and within the
somatodendritic cytoplasm in all major hippocampal regions, as well as in a
subset of dentate granule cell axons within the mossy fiber projection.
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