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This study combines detailed synapse resolution connectivity analysis with mapping of serotonin receptor expression to reveal an inhibitory subnetwork that is the target of serotonergic neurons within the olfactory system of Drosophila. Using neurophysiology and computational modeling, the differential effects of serotonin on this inhibitory subnetwork are posited to provide a mechanism for noise reduction in odor representations. 

The serotonergic system has been widely studied across animal taxa and different functional networks. This modulatory system is therefore well positioned to compare the consequences of neuromodulation for sensory processing across species and modalities at multiple levels of sensory organization. Serotonergic neurons that innervate sensory networks often bidirectionally exchange information with these networks but also receive input representative of motor events or motivational state. This convergence of information supports serotonin’s capacity for contextualizing sensory information according to the animal’s physiological state and external events. At the level of sensory circuitry, serotonin can have variable effects due to differential projections across specific sensory subregions, as well as differential serotonin receptor type expression within those subregions. Functionally, this infrastructure may gate or filter sensory inputs to emphasize specific stimulus features or select among different streams of information. The near-ubiquitous presence of serotonin and other neuromodulators within sensory regions, coupled with their strong effects on stimulus representation, suggests that these signaling pathways should be considered integral components of sensory systems.