The synaptic architecture of AMPA receptors at the cone pedicle of the primate retina

Cone pedicles, the output synapses of cone photoreceptors, transfer the lig ht signal onto the dendrites of bipolar and horizontal cells. Cone pedicles contain between 20 and 45 ribbon synapses (triads) which are the release s ites for glutamate, the cone transmitter. Several hundred postsynaptic dend rites contact individual cone pedicles, and we studied the glutamate recept ors expressed and clustered at these contacts, particularly the AMPA recept or subunits. Using immunocytochemistry and confocal imaging we were able to resolve indi vidual triads within the cone pedicles by light microscopy. We studied thei r differences in L/M- and S-cones, and we counted the number of triads per pedicle across the retina. The presynaptic matrix protein bassoon, the syna pse-associated membrane protein P84, and peanut agglutinin were used to spe cifically label synaptic ribbons, invaginating dendrites of horizontal cell s and invaginating dendrites of ON-cone bipolar cells, respectively. Pre- and post-embedding immunocytochemistry and electron microscopy were us ed to localize the AMPA receptor subunits at the cone pedicle base. They we re aggregated at three different postsynaptic sites: at horizontal cell inv aginating contacts, at bipolar cell flat contacts, and at desmosome-like ju nctions underneath the cone pedicles. We also performed double-labeling experiments with the triad-specific marke rs and the antibodies against the AMPA receptor subunits. AMPA receptors we re preferentially expressed by horizontal cells, and to a lesser extent by OFF-cone bipolar cells. We did not observe any cone-selective expression of AMPA receptor subunits postsynaptic to L/M- or S-cones, suggesting AMPA re ceptors are not the key to understanding trichromatic signaling in the prim ate retina.