Rod bipolar (RB) cells of the mammalian retina release glutamate in a grade
d, light-dependent fashion from 20 to 40 ribbon synapses (dyads). At the dy
ads, two classes of amacrine cells, the AI and AII cells, are the postsynap
tic partners. We examined the glutamate receptors (GluRs) that are expresse
d by AI and AII cells using immunocytochemistry with specific antibodies ag
ainst GluR subunits. Sections of macaque monkey and rabbit retina were exam
ined by confocal microscopy. AII amacrine cells were selectively labeled fo
r calretinin, and AI cells in rabbits were labeled for 5-HT uptake. Thus, d
ouble- and triple-labeling for these markers and GluR subunits was possible
. Electron microscopy using postembedding immunocytochemistry and double-la
beling was applied to show the synaptic expression of GluRs. We also studie
d the synaptic localization of the two postsynaptic density proteins PSD-95
and glutamate receptor-interacting protein (GRIP). We found that AII amacr
ine cells express the AMPA receptor subunits GluR2/3 and GluR4 at the RB ce
ll dyads, and they are clustered together with PSD-95. In contrast, AI amac
rine cells express the delta1/2 subunits that appear to be associated with
kainate receptor subunits and to be clustered together with GRIP. The RB ce
ll dyad is therefore a synapse that initiates two functionally and molecula
rly distinct pathways: a "through conducting" pathway based on AMPA recepto
rs and a modulatory pathway mediated by a combination of delta1/2 subunits
and kainate receptors.