The role of motor cortex in control of flight in the mammalian brain - Understanding the motor cortex's role in controlling complex, natural motor behaviors remain a major challenge in neuroscience, and thus limits our ability to elucidate mechanistic causes for many movement disorders. This proposal addresses a significant gap by introducing bat flight as a novel model to study motor control of natural dexterous movement. Traditional models often limit behavioral complexity and frequently require restraining and long training periods. As such, they may not fully explore the computational space of natural dexterous movements. In contrast, bat flight involves intricate 3D maneuvers requiring high precision and control over complex hand-like wings and is also naturally highly reproducible in the lab setting. This makes it an ideal paradigm for exploring motor cortical computations of complex natural behavior. To study this behavior in bats, we have recently made several key technological advancements. First, the use of wireless Neuropixels allows for the simultaneous recording of hundreds of neurons, providing unprecedented insight into population-level activity in freely flying bats. Second, the use of causal neuronal manipulation methods, such as optogenetics and chemogenetics, which allows for precise reversible perturbation at key points during flight. Our preliminary results indicate that motor cortex representations span several behaviorally relevant time scales, from the phase of the wingbeat cycle to the phase of the flight trajectory and to specific activity patterns for preparation / planning at the population-level. Using DREADDs, we find that motor cortex activity is crucial for precise flight control, with disruption leading to significant performance deficits. Thus, the integration of cutting-edge wireless recording technology and targeted neural manipulation offers innovative approaches to dissect motor control in freely flying bats. By characterizing flight behavior in both simple and obstacle-rich environments and mapping neuronal activity to these behaviors, this project aims to elucidate the motor cortical mechanisms underlying natural dexterous movement. This new research program studying motor control in bats has the potential to significantly enhance our understanding of motor cortex function and could uncover fundamental principles leading to translational applications that improve treatments and rehabilitation strategies for individuals with impaired motor function.
