Calcium channel levels at single synapses predict release probability and are upregulated in homeostatic potentiation

Communication in neural circuits depends on neurotransmitter release at specialized domains of presynaptic terminals called active zones. Evidence in multiple systems indicates that neurotransmitter release properties vary significantly, even between neighboring active zones of the same neuron. To investigate the role of voltage-gated calcium channels in determining diverse release properties, we combined endogenous tagging of the CaV2 channel Cacophony with functional imaging at Drosophila neuromuscular junctions. We find that calcium channels are differentially localized to active zones and robustly predict release probability at single synapses. Synaptic calcium channel levels, in turn, are highly correlated with ELKS/Bruchpilot levels at the active zone cytomatrix. During acute homeostatic potentiation, active zone cytomatrix remodeling is accompanied by a rapid increase in calcium channel levels. We propose that dynamic reorganization of the active zone cytomatrix during short-term plasticity generates new sites for the incorporation of calcium channels to modulate release properties and circuit function.