Distinct Developmental Mechanisms Act Independently to Shape Biased Synaptic Divergence from an Inhibitory Neuron

Neurons often contact more than one postsynaptic partner type and display stereotypic patterns of synaptic divergence. Such synaptic patterns usually involve some partners receiving more synapses than others. The developmental strategies generating "biased" synaptic distributions remain largely unknown. To gain insight, we took advantage of a compact circuit in the vertebrate retina, whereby the All amacrine cell (All AC) provides inhibition onto cone bipolar cell (BC) axons and retinal ganglion cell (RGC) dendrites, but makes the majority of its synapses with the BCs. Using light and electron microscopy, we reconstructed the morphology and connectivity of mouse retinal All ACs across postnatal development. We found that All ACs do not elaborate their presynaptic structures, the lobular appendages, until BCs differentiate about a week after RGCs are present. Lobular appendages are present in mutant mice lacking BCs, implying that although synchronized with BC axonal differentiation, presynaptic differentiation of the All ACs is not dependent on cues from BCs. With maturation, All ACs maintain a constant number of synapses with RGCs, preferentially increase synaptogenesis with BCs, and eliminate synapses with wide-field amacrine cells. Thus, All ACs undergo partner type-specific changes in connectivity to attain their mature pattern of synaptic divergence. Moreover, All ACs contact non-BCs to the same extent in bipolarless retinas, indicating that All ACs establish partner-type-specific connectivity using diverse mechanisms that operate in parallel but independently.