Converging preganglionic axons refine without synaptic transmission when targets downstream of sympathetic nerves are active

Abstract It is well accepted that refinement of converging presynaptic inputs depends on postsynaptic activity; however, it remains unclear how this developmental event is initiated. To address this, we developed a mosaic model where synaptically-active and synaptically-inactive sympathetic neurons develop side-by-side in the same ganglion. Surprisingly, we show that converging presynaptic inputs refine on neurons even without synaptic transmission as long as the synaptically-silent neurons share targets with synaptically-active neurons. In addition, our single-cell RNA sequencing experiments show that sympathetic ganglia contain at least 7 neuronal subtypes that decode the impact of synaptic activity differently, including their ability to maintain an adrenergic phenotype. Our results provide a new view on the roles that synaptic transmission and retrograde target activity have on developing circuits.