Transmission from the dominant input shapes the stereotypic ratio of photoreceptor inputs onto horizontal cells

Many neurons receive synapses in stereotypic proportions from converging but functionally distinct afferents. However, developmental mechanisms regulating synaptic convergence are not well understood. Here we describe a heterotypic mechanism by which one afferent controls synaptogenesis of another afferent, but not vice-versa. Like other CNS circuits, zebrafish retinal H3 horizontal cells undergo an initial period of remodeling, establishing synapses with UV and blue cones while eliminating red and green cone contacts. As development progresses, the horizontal cells selectively synapse with UV cones to generate a 5:1 UV-to-blue cone synapse ratio. Blue cone synaptogenesis increases in mutants lacking UV cones, and when transmitter release or visual stimulation of UV cones is perturbed. Connectivity is unaltered when blue cone transmission is suppressed. Moreover, there is no homotypic regulation of cone synaptogenesis by neurotransmission. Thus, biased connectivity in this circuit is established by an unusual activity-dependent, unidirectional control of synaptogenesis exerted by the dominant input.