The ability to move the body with skill and flexibility is a remarkable achievement of biological control, and the loss of this ability in disease or injury can be devastating. The neural circuits that control skilled movements are distributed broadly across the central nervous system and contain, in the mouse, tens of millions of functionally diverse neurons. Our central goals are to identify the principles governing the flow of neural activity across these large, distributed networks, to determine how these principles enable skilled motor control, and to discover how neural dynamics are altered in neurodegenerative diseases. To achieve these goals, we use high-density recording techniques to measure the activity of neural ensembles during natural movement, optogenetic approaches to manipulate this activity, and modern computational methods to extract models of the population dynamics from the resulting neurophysiological datasets.