Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina

The separation of OFF pathways that signal light decrements from ON pathways that signal light increments Occurs at the first retinal synapse. The dendrites of OFF bipolar cells abut the cone pedicle at basal positions distal to the site Of glutamate release and express ligand-gated or ionotropic glutamate receptors (GluR). The dendrites of ON bipolar cells penetrate narrow invaginations of the cone pedicle proximal to the site of release and express the G-protein-coupled, trietabotropic glutamate receptor, mGluR6. However, recent studies demonstrating the expression of GluR subunits in the rodent rod bipolar cell, known to yield all ON response to light, call this basic segregation of receptors into question. The light-microscopic distribution Of Many glutamate receptors in the primate retina is now well established. We reexamined their ultrastructural localization in the Outer retina of Macaca fascicularis to test systematically whether invaginating dendrites at the cone synapse, presumably from ON bipolar cells, also express one or more ionotropic Subunits. Using preembedding immunocytochemistry for electron microscopy, we quantified the distribution of the AMPA-sensitive Subunits GluR2/3 and GluR4 and of the kainate-sensitive Subunits GluR6/7 across 207 labeled dendrites occupying specific morphological loci at the cone pedicle. We report, in agreement with published investigations, that the majority of labeled processes for GluR2/3 (70%) and GluR4 (67%) either Occupy basal positions or arise from horizontal cells. For GluR6/7, we find a significantly lower fraction of labeled processes at these positions (47%). We also find a considerable number of labeled dendrites for GluR2/3 (10%), GluR4 (21%), and GluR6/7 (18%) at invaginating positions. Surprisingly, for each subunit, the remainder of labeled processes corresponds to fingers of presynaptic cytoplasm within the cone invagination.