SYNAPTIC DISTRIBUTION OF GLUR2 IN HIPPOCAMPAL GABAERGIC INTERNEURONS AND PYRAMIDAL CELLS - A DOUBLE-LABEL IMMUNOGOLD ANALYSIS

GluR2 is the regulatory subunit in the AMPA family of glutamate recept ors (GluRs) in that its presence inhibits calcium flux and dominates t he current/voltage characteristics of AMPA receptors. Studies from oth er laboratories have shown that GABAergic interneurons have a lower ra tio of GluR2/GluR1 mRNA than pyramidal cells as well as possessing AMP A receptors that have a higher relative permeability to calcium. We hy pothesized that such differences might be related to differences in th e subunit stoichiometry at the AMPA synapses in each cell class, and u sed a GluR2-specific monoclonal antibody in a double-label immunogold protocol with anti-GABA and anti-CaM kinase II to compare the GluR2 re presentation at asymmetric synapses in GABA neurons to that of pyramid al cells in rat CA1. Virtually all CA1 pyramidal cells as well as the majority of GABAergic interneurons were GluR2 positive. EM. immunogold labeling also showed that GABAergic interneurons had distinctive ultr astructural features and contained GluR2 in both their soma and their dendrites, as did the spines and shafts of pyramidal cells. GluR2 immu noreactivity was frequently preferentially located at asymmetric synap ses on both pyramidal cell spines and shafts as well as the dendritic processes and soma of GABAergic interneurons. However, the labeled syn apses on GABAergic neurons had a significantly lower number of immunog old particles than those on pyramidal cells. In fact, 90% of the label ed asymmetric synapses on GABAergic cells had one to three gold partic les, whereas greater than 70% of the labeled asymmetric synapses on py ramidal cells had four or more gold particles associated with the syna pse. These data suggest that while both cell classes contain GluR2, th ey differ in the relative representation of GluR2 at their AMPA synaps es, such that GABAergic neurons might possess AMPA receptors with high er calcium permeability on average than pyramidal cells. Such differen ces in subunit representation at AMPA-receptor-mediated synapses would not only lead to differences in calcium permeability and functional c haracteristics across these two cell classes, but might also be releva nt to the hippocampal patterns of selective vulnerability with respect to excitotoxicity and neurodegeneration. (C) 1998 Academic Press.