PROJECT SUMMARY. The nervous system constantly adjusts how it processes sensory information based on the experience and physiological state of an animal. This flexibility is enabled by the release of neuromodulators, which alter the biophysical properties and synaptic interactions between neurons within a network. Neuromodulatory dysfunction is associated with many neurological disorders, yet despite its importance for healthy sensory processing, the effects of neuromodulation on sensory processing are often heterogeneous and difficult to predict. This is due to the diversity of receptors for a given neuromodulator, and the complexity of cell-class specific receptor expression patterns. For example, there are 14 serotonin receptors that differ in their intracellular signaling targets, time course of action and binding affinity for serotonin. When this is combined with the diversity of cell types within a neural network, understanding the impact of serotonin on sensory processing becomes challenging. We propose to address the topic of the receptor basis sensory modulation using the olfactory system of Drosophila as there is comprehensive understanding of sensory network connectivity and the modulatory receptors expressed by each class within that network. We previously demonstrated that serotonergic neurons primarily synapse upon inhibitory neurons that affect different aspects of olfactory coding in Drosophila. Our objective is to determine how the serotonin receptors expressed by each class of inhibitory neuron alter olfactory coding and odor-guided behavior. Our proposed experiments will establish how receptor expression patterns dictate the effects of serotonin on information coding, thus addressing a critical gap in our knowledge of healthy sensory processing. Ultimately this will reveal the mechanisms by which serotonin regulates how information about the external world is processed.