UCLA

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing in the face of a highly variable stimulus space. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. The role for serotonergic signaling in the Drosophila optic lobe and the mechanisms by which serotonin regulates visual neurons remain unclear. Here we map the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina, and show that serotonin can modulate visual responses. Serotonin receptors are expressed in several types of columnar cells in the lamina including 5 HT2B in lamina monopolar cell L2, required for the initial steps of visual processing, and both 5 HT1A and 5 HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5 HT2B and 5 HT1A constructs indicates that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla is the primary site of serotonergic regulation for these neurons. Serotonin increases intracellular calcium in L2 terminals in layer M2 and alters the kinetics of visually induced calcium transients in L2 neurons following dark flashes. These effects were not observed in flies without functional 5-HT2B, which displayed severe differences in the amplitude and kinetics of their calcium response to both dark and light flashes. While we did not detect serotonin receptor expression in L1 neurons, they also undergo serotonin-induced calcium changes, presumably via cell non-autonomous signaling pathways. We provide the first functional data showing a role for serotonergic neuromodulation of neurons required for initiating visual processing in Drosophila. These findings demonstrate that tracing the molecular mechanisms of serotonergic modulation require a combination of receptor mapping to individual cells and subcellular compartments with complementary functional assays. We have identified a testable model system for these studies and developed new tools for studying the serotonin transporter.