Corticospinal neurons in response control and movement coordination

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To navigate through our ever-changing environment, we must continually process sensory information to make informed decisions and execute goal-oriented movements. This process of generating 'goal appropriate' actions whilst avoiding 'inappropriate' or unwanted actions is known as response control and is an essential component of everyday life necessary for our survival. Think of a fighter pilot on a low flying exercise through a mountainous area. The pilot uses all her available senses, visual flow, acoustic indicators, and proprioceptive feedback to ensure that she generates purposive voluntary movements of the control stick with the goal of selecting the appropriate flight path out of the mountains. All the while suppressing unwanted movements that would have significant and unwanted consequences. Central to the process of response control and movement coordination is an area of the brain known as the motor cortex which contains thousands of neurons (i.e., electrically excitable cells that convey information around the nervous system) that ultimately generate the 'command' signals that drive our muscles and help us move. Embedded within motor cortex are a particular type of output neuron named corticospinal neurons (CSNs) which send projections from the brain to the spinal cord to directly influence muscle activation. Despite decades of intensive investigation of the motor system, we still do not fully understand how thousands of CSNs organise their activity in time and space to generate efficient response control and coordination of our limbs during goal-directed movements. Previous work has shown that changes in the activity of single CSNs occur during the period when movement selection occurs, the so-called movement preparation phase, and throughout movement execution. Most CSNs show movement-related increased activity consistent with the generation of descending motor commands necessary for muscle activation. However, a significant proportion of CSNs display reduced activity during the same period, suggesting bidirectional changes in CSN output may be a prerequisite for efficient selection and execution of voluntary movements. These early correlative studies provided the first evidence that CSNs play an important role in motor control, but we lack a deeper understanding of how CSN activity is organised across motor cortex, how inputs to these neurons influence or shape their activity over time and how blocking of CSN output affects response control and movement coordination.To address this, we will train mice to perform an auditory cued motor task where the goal is to move a joystick to either a forward or backward reward zone (think of the fighter pilot analogy above) to receive a fluid reward. This goal-oriented task allows the exploration of both response control and movement coordination. We will use a combination of different brain recording techniques combined with approaches to manipulate the activity of neurons in real-time to try and understanding how dense populations of CSNs organise their activities during task execution and the importance of these patterns of activity for efficient task completion. Our findings will have important implications for understanding how CSNs execute appropriate movement of our limbs constituting an important step towards refining current theories of motor control.