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.
Dopamine organizes motor sequences and signals expectation of reward in humans, while disruptions of dopamine signaling contribute to addiction and movement disorders. Since there are many different populations of dopaminergic neurons in the human brain, each with complex projections and potentially different functions, it is challenging to deduce general principles about how dopamine works at the behavioral, circuit, and cellular levels. The experiments proposed here use a simpler animal, the fruit fly, to address the way specific dopaminergic neurons form circuits that modulate sensory inputs and control the progression of a motor sequence to uncover basic knowledge about how the nervous system controls behavior generally and how dopamine functions specifically.
