Inhibitory control of locomotor statistics in walking Drosophila

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior over time, for example switching between long-range dispersal behaviors and more localized search depending on the availability of resources. How pre-motor circuits regulate such locomotor statistics is not clear. Here we took advantage of the robust changes in locomotor statistics evoked by attractive odors in walking Drosophila to investigate their neural control. We began by analyzing the statistics of ground speed and angular velocity during three well-defined motor regimes: baseline walking, upwind running during odor, and search behavior following odor offset. We find that during search behavior, flies adopt higher angular velocities and slower ground speeds, and tend to turn for longer periods of time in one direction. We further find that flies spontaneously adopt periods of different mean ground speed, and that these changes in state influence the length of odor-evoked runs. We next developed a simple physiologically-inspired computational model of locomotor control that can recapitulate these statistical features of fly locomotion. Our model suggests that contralateral inhibition plays a key role both in regulating the difference between baseline and search behavior, and in modulating the response to odor with ground speed. As the fly connectome predicts decussating inhibitory neurons in the lateral accessory lobe (LAL), a pre-motor structure, we generated genetic tools to target these neurons and test their role in behavior. Consistent with our model, we found that activation of neurons labeled in one line increased curvature. In a second line labeling distinct neurons, activation and inactivation strongly and reciprocally regulated ground speed and altered the length of the odor-evoked run. Additional targeted light activation experiments argue that these effects arise from the brain rather than from neurons in the ventral nerve cord, while sparse activation experiments argue that speed control in the second line arises from both LAL neurons and a population of neurons in the dorsal superior medial protocerebrum (SMP). Together, our work develops a biologically plausible computational architecture that captures the statistical features of fly locomotion across behavioral states and identifies potential neural substrates of these computations.