Connectivity of serotonin neurons reveals a constrained inhibitory subnetwork within the olfactory system.

Inhibitory local interneurons (LNs) play an essential role in sensory processing by refining stimulus representations via a diverse collection of mechanisms. The morphological and physiological traits of individual LN types, as well as their connectivity within sensory networks, enable each LN type to support different computations such as lateral inhibition or gain control and are therefore ideal targets for modulatory neurons to have widespread impacts on network activity. In this study, we combined detailed connectivity analyses, serotonin receptor expression, neurophysiology, and computational modeling to demonstrate the functional impact of serotonin on a constrained LN network in the olfactory system of Drosophila. This subnetwork is composed of three LN types and we describe each of their distinctive morphology, connectivity, biophysical properties and odor response properties. We demonstrate that each LN type expresses different combinations of serotonin receptors and that serotonin differentially impacts the excitability of each LN type. Finally, by applying these serotonin induced changes in excitability to a computational model that simulates the impact of inhibition exerted by each LN-type, we predict a role for serotonin in adjusting the dynamic range of antennal lobe output neurons and in noise reduction in odor representations. Thus, a single modulatory system can differentially impact LN types that subserve distinct roles within the olfactory system. Significance StatementInhibitory interneurons refine information processing within sensory networks by enforcing distinct local computations. They are therefore ideal targets for modulatory neurons to efficiently alter sensory processing by up- or downregulating the computations each interneuron class subserves. We identify an interconnected network of three interneuron types in the olfactory system of Drosophila that receive a large amount of serotonergic synaptic input. Each interneuron type differs in their biophysical and response properties and serotonin differentially impacts their excitability. Finally, using a computational model, we predict that the combined effects of serotonin on these inhibitory neurons enables noise reduction in the olfactory system. Thus, modulation of individual cell types collectively adjusts distinct network computations to enable flexible sensory coding.