Project Summary Dopamine is a critical neurotransmitter and neuromodulator that governs essential neural circuits and behaviors. It has been implicated in human motor syndromes from Parkinson’s Disease to Obsessive-Compulsive Disorder, but its mechanism of action is not fully understood. Alterations in dopamine signaling affect fly grooming behavior, which is also a complex motor sequence. This discovery opens the door to using the exceptional experimental advantages of this organism to address fundamental open questions. The ability to manipulate small numbers of dopaminergic neurons, measure behavioral consequences, and visualize neural connectivity and activity make fly grooming an excellent model to better understand the action of dopamine at molecular, subcellular, cellular, circuit, and organismal levels. We propose behavioral experiments to determine how dopamine affects the fine structure of an innate, modular motor sequence, where it may enable flexibility based on internal state and changing sensory stimuli. We also propose anatomical characterization of dopaminergic neurons in the ventral nerve cord and their synaptic partners to identify circuit motifs that modify sensory neuron activity. These experiments test the hypothesis that dopamine sustains neural activity in mechanosensory bristle neurons, leading to useful behavioral persistence during grooming. This mechanism may explain more generally how dopamine contributes to motor control and action sequence organization.