Combinations of AMPA Receptor Subunit Expression in Individual Cortical Neurons Correlate with Expression of Specific Calcium-Binding Proteins

Abstract

The functional properties of AMPA-type glutamate receptors are determined by their subunit composition. We detected the expression of the AMPA receptor subunits (GluR1-GluR4) in neurons in the somatosensory cortex of adult rats by combining nonradioactive in situ hybridization using digoxigenin-labeled RNA probes of GluR1 and GluR2 with immunocytochemistry using specific antibodies against GluR1, GluR2/3, and GluR4. On the basis of differential expression of the GluR1 and GluR2 subunits, we classified the cortical neurons into four categories. To correlate the differential expression of AMPA receptor subunits in each neuron with that of two calcium-binding proteins, parvalbumin and calbindin-D28k, we used a triple-labeling method. The majority of cortical neurons (ϳ2/3) showed expression of GluR2 and undetectable expression of GluR1. GluR1-/GluR2-expressing neurons and GluR1-expressing/GluR2-undetectable neurons comprised ϳ1/10 each. Regarding the morphology, most GluR1-undetectable/GluR2-expressing neurons were pyramidal cells in layers II/III, V, and VI, whereas most GluR1-expressing/GluR2-undetectable neurons were nonpyramidal cells in layers II-VI. The GluR1-/GluR2-expressing neurons were either pyramidal or nonpyramidal. The majority of GluR1-/GluR2-expressing nonpyramidal cells was intensely stained with monoclonal antibody against calbindin-D28k, and one-half of the GluR1-undetectable/GluR2-expressing pyramidal neurons in layer II/III were lightly stained with this antibody. Most of GluR1-expressing/GluR2-undetectable neurons possessed parvalbumin immunoreactivity. These results indicate that neurons in the rat somatosensory cortex express differential combinations of GluR subunits, which correlate with the specific expression of the calcium-binding proteins.

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

“…Whereas a minority of GABAergic interneurons express GluR-B at levels comparable with pyramidal cells (34), in most GABAergic interneurons this subunit is expressed at significantly lower levels. This expression pattern has been documented by in situ hybridization (35)(36)(37) and immunocytochemistry (34,(38)(39)(40)(41). Low GluR-B expression in GABAergic cells affects a number of AMPA receptor properties, including Ca 2ϩ permeability (31,32,42,43), block by polyamines (44), and single-channel conductance (22), and is the molecular basis for certain novel forms of plasticity (44)(45)(46).…”

A neurochemical signature of visual recovery after extrastriate cortical damage in the adult cat

“…Previous reports in rodents (Geiger et al, 1995;Vissavajjhala et al, 1996;Angulo et al, 1997;Kondo et al, 1997) and primates (Vickers et al, 1993;Munoz et al, 1999) suggest that some classes of cortical neurons, including those expressing calcium-binding proteins, can be differentiated by their expression of different AMPA receptor subunits. However, our present experiments revealed that in normal cats, the great majority of calbindin-and parvalbuminpositive cells, and the majority of LS-projecting pyramidal cells in layer II/III of area 18 expressed all four subunits of the AMPA receptor.…”

“…They are comprised of four subunits-GluR1, GluR2, GluR3, and GluR4-that are differentially expressed in different neurons (Vickers et al, 1993;Geiger et al, 1995; Vissavaijhala et al, 1996;Angulo et al, 1997;Kondo et al, 1997;Munoz et al, 1999;Van Damme et al, 2003). Although many glutamate receptors (such as AMPA, N-methyl-D-aspartate [NMDA], kainate) play a role in activity-dependent neuronal plasticity (Collingridge and Singer, 1990;Malenka and Nicoll, 1993), the sensitivity of AMPA receptor to changes in connectivity and function within the cat visual system has been well demonstrated (Gordon et al, 1996;Price and Huxlin, 2001;Van Damme et al, 2003).…”

Differential localization of the GluR1 and GluR2 subunits of the AMPA-type glutamate receptor among striatal neuron types in rats

“…While the high spike rate of these neurons upon depolarization appears to reflect an intrinsic membrane property, their relative enrichment in cortical input and AMPA receptors accounts for their robust responses to cortical activation. Moreover, their specific enrichment in GluR1 and GluR4 compared to GluR2 (Martin et al, 1993b;Tallaksen-Greene and Albin, 1994;Chen et al, 1996;Bernard et al, 1997;Kwok et al, 1997) explains their inwardly rectifying I-V curve (Koos and Tepper, 1999), and indicates they are likely to mainly possess AMPA receptors with high calcium permeability, as typically true of PARV+ telencephalic neurons (Geiger et al, 1995;Götz et al, 1997;Kondo et al, 1997;Washburn et al, 1997). The higher single-channel conductance and faster desensitization of GluR1/4-rich AMPA receptors may also help explain the robust short duration action potentials in response to cortical activation (Kawaguchi, 1993;Koos and Tepper, 1999).…”