Intrinsic diversity in odor-evoked calcium rises across Drosophila olfactory neurons

Across species, olfactory receptor neurons (ORNs) exhibit stimulus-driven changes in gene expression, with calcium as a key activity signal. However, it remains unclear whether neuronal activity elevates intracellular calcium with differential gain across ORN types, which could then disparately influence a neuron’s propensity for activity-dependent modulation. To address this possibility, we combined simultaneous electrophysiology and calcium imaging to systematically map odor-evoked calcium gain across the majority of characterized Drosophila ORN types of either sex. Despite comparable spike rates, calcium signals can differ by more than tenfold. Within each ORN, calcium scaled linearly with spiking, yet the slope varied markedly across neuron types. Mechanistically, calcium gain was intrinsic to ORN type, independent of receptor identity, and differentially regulated in distinct ORNs by internal calcium store and voltage-dependent calcium entry. These findings reveal striking heterogeneity in odor-evoked calcium gain, with implications for how individual ORNs interpret odor activation to differentially engage activity-dependent processes and plasticity. Significance statement Our study assayed the majority of Drosophila olfactory receptor neurons using simultaneous electrophysiology and calcium imaging. Using spike activity as the ground truth, we found strikingly diverse, cell type-specific calcium rises across the ORN repertoire. Mechanistically, cell-specific genetic manipulations revealed distinct channel requirements for spike-to-calcium coupling, independent of receptor identity. Given calcium’s role as a central signaling molecule in transduction, plasticity, and numerous other cellular processes, defining how spikes translate into calcium signals across neuron types provides essential insight into how olfactory neurons interpret odor activation and engage activity-dependent processes.