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 receptors (GluRs) in that its presence inhibits calcium flux and dominates the current/ voltage characteristics of AMPA receptors. Studies from other laboratories have shown that GABAergic interneurons have a lower ratio of GluR2/GluR1 mRNA than pyramidal cells as well as possessing AMPA receptors that have a higher relative permeability to calcium. We hypothesized that such differences might be related to differences in the subunit stoichiometry at the AMPA synapses in each cell class, and used a GluR2-specific monoclonal antibody in a double-label immunogold protocol with anti-GABA and anti-CaM kinase II to compare the GluR2 representation at asymmetric synapses in GABA neurons to that of pyramidal 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 ultrastructural features and contained GluR2 in both their soma and their dendrites, as did the spines and shafts of pyramidal cells. GluR2 immunoreactivity was frequently preferentially located at asymmetric synapses on both pyramidal cell spines and shafts as well as the dendritic processes and soma of GABAergic interneurons. However, the labeled synapses on GABAergic neurons had a significantly lower number of immunogold particles than those on pyramidal cells. In fact, 90% of the labeled asymmetric synapses on GABAergic cells had one to three gold particles, whereas greater than 70% of the labeled asymmetric synapses on pyramidal cells had four or more gold particles associated with the synapse. These data suggest that while both cell classes contain GluR2, they differ in the relative representation of GluR2 at their AMPA synapses, such that GABAergic neurons might possess AMPA receptors with higher calcium permeability on average than pyramidal cells. Such differences in subunit representation at AMPA-receptor-mediated synapses would not only lead to differences in calcium permeability and functional characteristics across these two cell classes, but might also be relevant to the hippocampal patterns of selective vulnerability with respect to excitotoxicity and neurodegeneration.