Stimulus-Specific Modulation is Enabled by Differential Serotonin Receptor Expression

Neural networks must be able to flexibly process information under different conditions. To this end, networks frequently rely on uniform expression of modulatory receptors by distinct classes of neurons to fine tune the computations supported by each neuronal class. In this study, we explore the consequences of heterogeneous, rather than uniform, serotonin (5-HT) receptor expression within a cell class for olfactory processing in Drosophila melanogaster. Here, we demonstrate that two distinct populations of olfactory output neurons (projection neurons, PNs) display heterogeneous receptor co-expression of all 5-HT receptors. Moreover, the PN populations that express distinct 5-HT receptors innervate different combinations of glomeruli, implying that the effects of 5-HT on these PNs may vary with their odor tuning. Furthermore, connectomic analyses reveal that PN subsets with different receptor profiles have little convergence upon downstream synaptic partners. Finally, 5-HT differentially modulates the odor-evoked responses of PNs with distinct receptor expression profiles and odor tuning. Overall, this implies that heterogeneous modulatory receptor expression enables differential tuning of activity within a neuronal class depending on the odor scene to which individual neurons respond.