Periodic Reporting for period 1 - DeCoDr (Descending Control of Motor Circuits in Drosophila)
Reporting period: 2023-05-01 to 2025-04-30
Understanding how neural circuits control arm and leg movements is a major challenge in neuroscience with implications for treating movement disorders, designing neural prostheses, and robotics. Even seemingly simple, everyday movements such as walking rely on the integrated activity of complex circuits that span multiple levels of the nervous system. High-level circuits in the brain generate movement instructions, such as when to start moving and how fast to move. Low-level circuits in the spinal cord (in vertebrates) or ventral nerve cord (in invertebrates) integrate these instructions to generate appropriate activation patterns for muscles. The instructions are encoded by a small number of descending neurons, which form a critical link between the brain and the body. In this project, we addressed two major open questions related to descending neurons: how brain circuits are organized to recruit descending neurons for a specific motor task in a context-appropriate manner, and how low-level circuits translate descending neuron instructions into coordinated limb movement. To tackle these questions, we took advantage of the powerful experimental tools available for the compact nervous system of the fruit fly, Drosophila melanogaster, including connectomics, optogenetics, and neural recordings in behaving animals. The fly’s neural circuits controlling the limbs are more tractable and experimentally accessible than those of vertebrates, but still similar in their basic organization and function. This suggests that the motor control principles discovered in the fly will be highly relevant to motor control in other animals, including mammals.
To better understand how descending neurons are recruited for a specific motor task, we first identified higher-level neurons in the fly brain that encode specific movement instructions. In particular, we identified neurons that control the initiation of walking and walking speed. The identified neurons are sufficient and necessary for fast walking, they are recruited specifically during spontaneous walking, and they control walking speed independently of direction. We found that these neurons are part of a larger, multi-layered speed control circuit in the brain, whose outputs converge onto a specific population of descending neurons. These descending neurons in turn target complex networks of premotor neurons in the ventral nerve cord, which are positioned to translate the descending speed signals into coordinated limb movement. We further found that the speed signals from the brain support goal-directed locomotion rather than overriding it, suggesting that the multi-layered circuit architecture ensures that speed signals are integrated appropriately according to the behavioral context and goals. Together, these findings elucidate how the brain channels specific movement instructions (walking speed) into descending neurons to engage pattern-generating circuits in the nerve cord.
Our findings provide new insight into a fundamental question in neuroscience with scientific impact beyond the scope and duration of the project. For example, our findings set the stage for investigating how specific premotor neurons in the nerve cord transform descending movement instructions into coordinated limb movement. Moreover, the identified speed control circuit in the brain may inform ongoing efforts in the community to build realistic neuromechanical simulations of Drosophila. Finally, the speed control neurons identified in the fly brain show striking similarities with neurons previously identified in the brainstem of rodents. Future research comparing flies and rodents will allow us to test how different nervous systems solve analogous motor control challenges, while also identifying general principles. To facilitate this research, our results are anchored in the connectomes of the fly brain and nerve cord, and all data and code will be published open access.