CAREER: High-level control of low-level circuits in the mammalian motor system

All behavior – everything that an animal does – is defined by their movements. As a result, the control of flexible, dexterous, goal-directed movements is one of the most important functions of the nervous system. Motor circuits in the vertebrate brain are arranged hierarchically. Low-level circuits in the brainstem and spinal cord – such as the central pattern generators that control breathing and locomotion – can autonomously produce basic motor patterns. High-level motor circuits allow animals to learn and adapt movements, detect and correct errors, predict the cost and benefits of actions, and assemble movements into complex sequences to attain behavioral goals over long time scales. High-level circuits do not generally control movements directly, but, instead, engage and modify the basic motor programs produced by low-level circuits. Low-level circuits in turn integrate an array of inputs from many high-level areas to synthesize the motor commands that drive motor neurons and muscles. Little is currently known about how a multitude of high-level motor centers together control low-level circuits in a coordinated fashion, despite the centrality of this process to all flexible behavior. The overarching goal of this project is to identify how high-level regions of the mouse motor system turn on, turn off, and modify the motor patterns produced by low-level circuits. Critically, tackling this problem will differentiate between two competing models of hierarchical control that may be utilized in the mammalian brain. In the Cooperative model, there exists a ‘division of labor’ between high-level motor centers with different circuits responsible for different computational processes – any or all of which may be invoked simultaneously according to behavioral demands. Alternatively, the Parallel model predicts that many high-level brain regions are equally capable of commanding movements in their entirety, with different regions subsuming control in the behavioral context for which they are specialized. This project leverages a cutting-edge experimental toolkit in mice for manipulating neural activity and tracking the signals communicated between them with cell-type specificity. This project focuses on control of a well-defined central pattern generator responsible for controlling tongue movements in mice to leverage a novel paradigm in which mice perform the same tongue movements in contexts associated with different high-level control processes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.