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bioRxiv · 10.1101/2025.03.21.644681

Serotonin selectively modulates visual responses of object motion detection in Drosophila

Bertsch, D. J.·Palacios Castillo, L. M.·Frye, M. A.
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Abstract

Serotonin (5-HT) is a hormonal messenger that confers state-level changes upon the nervous system in both humans and flies. In Drosophila, lobula columnar (LC) cells are feature-detecting neurons that project from the optic lobe to the central brain, where each population forms an anatomically-distinct glomerulus with heterogeneous synaptic partners. Here, we investigated serotonins effect on two LC populations with different 5-HT receptor expression profiles. Receptor expression does not predict neuromodulatory effects: LC15 expresses inhibitory 5-HT1A and 5-HT1B receptors, yet serotonin increases the amplitude of calcium responses to visual stimuli. LC12 expresses inhibitory 5-HT1A and excitatory 5-HT2A receptors, yet serotonin application does not influence visual responses. Serotonin targets select visual response properties, potentiating LC15 responses to a motion-defined bar and tuning the gain of responses to varying object velocity but has no influence on contrast sensitivity. Serotonin does not significantly facilitate LC15 responses in postsynaptic dendrites, only in the presynaptic terminals of the glomerulus, which suggests that the neuromodulatory effects are strongest in the central brain. Connectomics confirms that LC12 and LC15 share neither presynaptic inputs nor postsynaptic outputs in the central brain. The wiring diagram shows no synaptic interactions between the LC15 circuit and major serotonergic 5-HTPLP neurons, nor to other serotonergic neurons of the central brain, suggesting that endogenous 5-HT acts via paracrine transmission on non-serotonergic pathways. Lobula- and glomerulus-specific GABAergic and glutamatergic inhibitory partners, positioned to filter visual stimuli, are putative 5-HT targets. These results provide a comparative framework for the neuromodulatory mechanisms involved in visual processing. New & NoteworthyHow does neuromodulatory state affect visual feature detection? In this work, we demonstrate highly specific facilitated visual responses of object-detecting neurons after serotonin bath application in Drosophila. Serotonin potentiates motion-defined bar responses in object-detecting LC15 neurons and tunes response gain to translating bars of mid-range velocities in presynaptic axon terminals. Our calcium imaging extends what is known about extra-synaptic neuromodulation in the visual system and shows that serotonin heightens visual processes that inform object-specific behavior.

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Bertsch, D. J., Palacios Castillo, L. M., Frye, M. A.. 2025-03-24. Serotonin selectively modulates visual responses of object motion detection in Drosophila. https://doi.org/10.1101/2025.03.21.644681

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