Synaptic density and relative connectivity conservation maintain circuit stability across development

Abstract

As bodies grow during postembryonic and postnatal development, nervous systems must expand to preserve circuit integrity. To investigate how circuits retain stable wiring and function throughout development, we combined synaptic-level resolution electron microscopy (EM) with computational modeling in the Drosophila larval nociceptive system. Based on EM data, we generated the "contactome"--the set of synaptic membrane contacts--of this circuit across development to evaluate how different mechanisms contribute to wiring stability. Specifically, we investigated three mechanisms: correlation-based plasticity and synaptic scaling, which modify synaptic strength, and structural plasticity, which preserves synaptic density. We found that synaptic sizes remain largely stable across development, and synapses between the same pre- and postsynaptic neurons do not correlate in size, suggesting that synaptic scaling and correlation-based plasticity play a limited role in shaping connectivity. In contrast, dendritic synaptic density remains invariant despite a previously reported fivefold increase in neuron size and synapse number. This conservation requires increased axonal presynaptic density to compensate for unequal axonal and dendritic growth. As neurons grow, this adjustment is necessary to maintain the relative synaptic input associated with each presynaptic partner across development. Our EM analysis and modeling show that conserving relative connectivity and synaptic density is sufficient to maintain consistent postsynaptic responses across development, highlighting these conserved structural features as key contributors to circuit stability during growth.