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 a 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 and establish a new platform for investigating the serotonergic neuromodulation of sensory networks.Author SummarySerotonergic neurons innervate the Drosophila melanogaster eye, but the function of serotonergic signaling is not known. We found that serotonin receptors are expressed in all neuropils of the optic lobe and identify specific neurons involved in visual information processing that express serotonin receptors. We then demonstrate that activation of these receptors can alter how visual information is processed. These are the first data suggesting a functional role for serotonergic signaling in Drosophila vision. This study contributes to the understanding of serotonin biology and modulation of sensory circuits.

The optokinetic nystagmus is a gaze-stabilizing mechanism reducing motion blur by rapid eye rotations against the direction of visual motion, followed by slower syndirectional eye movements minimizing retinal slip speed. Flies control their gaze through head turns controlled by neck motor neurons receiving input directly, or via descending neurons, from well-characterized directional-selective interneurons sensitive to visual wide-field motion. Locomotion increases the gain and speed sensitivity of these interneurons, while visual motion adaptation in walking animals has the opposite effects. To find out whether flies perform an optokinetic nystagmus, and how it may be affected by locomotion and visual motion adaptation, we recorded head movements of blowflies on a trackball stimulated by progressive and rotational visual motion. Flies flexibly responded to rotational stimuli with optokinetic nystagmus-like head movements, independent of their locomotor state. The temporal frequency tuning of these movements, though matching that of the upstream directional-selective interneurons, was only mildly modulated by walking speed or visual motion adaptation. Our results suggest flies flexibly control their gaze to compensate for rotational wide-field motion by a mechanism similar to an optokinetic nystagmus. Surprisingly, the mechanism is less state-dependent than the response properties of directional-selective interneurons providing input to the neck motor system.