Descripción del proyecto
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. Limb movements are coordinated by low-level motor circuits in the spinal cord (in vertebrates) or ventral nerve cord (in invertebrates), which receive movement instructions from the brain via a small number of descending neurons (DNs). DNs constitute the critical link between the brain and the body. However, despite their importance, little is known about how specific DNs are recruited depending on the behavioral context, and how low-level motor circuits in the spinal cord or ventral nerve cord translate DN activity into limb movement. I propose leveraging cutting-edge tools to tackle these fundamental questions in the compact nervous system of the fruit fly, Drosophila melanogaster. The fly’s neural circuits for controlling limbs are more tractable and experimentally accessible than those of vertebrates, but still similar in their organization and function. Focussing on DNs that have been implicated in the control of walking speed, I will characterize the activity of DNs during behavior, identify the target neurons of DNs in motor circuits in the ventral nerve cord, and quantify the influence of DNs on these target neurons. By combining intracellular patch-clamp recordings, calcium imaging, and movement tracking in behaving animals with computational modeling and connectomics, the proposed research project will provide unique mechanistic insight into the interactions between the brain and low-level motor circuits that have remained elusive in other animals.