Hierarchical partner selection shapes rod-cone pathway specificity in the inner retina

Neurons form stereotyped microcircuits that underlie specific functions. In the vertebrate retina, the primary rod and cone pathways that convey dim and bright light signals, respectively, exhibit distinct wiring patterns. Rod and cone pathways are thought to be assembled separately during development. However, using correlative fluorescence imaging and serial electron microscopy, we show here that cross-pathway interactions are involved to achieve pathway-specific connectivity within the inner retina. We found that A17 amacrine cells, a rod pathway-specific cellular component, heavily bias their synaptogenesis with rod bipolar cells (RBCs) but increase their connectivity with cone bipolar cells (CBCs) when RBCs are largely ablated. This cross-pathway synaptic plasticity occurs during synaptogenesis and is triggered even on partial loss of RBCs. Thus, A17 cells adopt a hierarchical approach in selecting postsynaptic partners from functionally distinct pathways (RBC>CBC), in which contact and/or synaptogenesis with preferred partners (RBCs) influences connectivity with less-preferred partners (CBCs).