Descripción del proyecto
Understanding how neuronal circuits regulate the enormous repertoire of movements is a key outstanding question in neuroscience. Neurons contributing to execution and learning of body movements are distributed throughout the nervous system. Control of body movements entails the engagement of connected brain motor centers to generate action commands, providing instructions for execution to the spinal cord. The brainstem as focus of this proposal represents an essential intermediary between upper planning and spinal executive motor circuits. Recent technological advances have led to the identification of brainstem neurons regulating diverse forms of body movement, including locomotion and skilled forelimb movements, both engaging limbs but for very distinct purposes. The goal of this project is to understand how brainstem populations involved in specific body movements are endowed with their behavior-specific fingerprints through interactions within the broader motor system. We aim to determine how key synaptic inputs to specific brainstem neurons shape their activity patterns in synchrony with the regulated behavior. We hypothesize that the emergence of action-specific neuronal ensembles in the brainstem requires control by their driver, gating and modulatory elements, with the function to promote the recruitment of specific brainstem neurons during desired actions and to suppress them when no or alternative actions are planned. We build on our know-how on brainstem neurons and use sophisticated combinatorial viral-genetic targeting strategies, state of the art neuronal recording and activity-pattern modifying technologies, combined with precise quantitative behavioral readouts in mice to address this question. Together, our project will elucidate circuit mechanisms by which brainstem neurons interact in the motor system to control the generation of body movements, thereby uncovering principles of how the nervous system generates diverse actions.