This is a proposal to map the “connectome” of the primate fine motor control system. This work has the potential to lead to a new and remarkably detailed understanding of anatomical mechanisms underlying corticospinal fine motor control in primates, as well as reorganization of motor systems after injury that are associated with functional loss and recovery. Aim 1: The Intact Primate Corticospinal Connectome Aim 1 will map the intact corticospinal connectome underlying hand control in the rhesus monkey using new viral tools. These viral tools will identify all projections and collateral branches arising from corticospinal neurons that project to C8 spinal cord segments to influence fine motor control of the hand. Unprecedented detail and specificity will be achieved using efficient retrograde transport of AAV9-Cre injected into spinal segment C8, and motor cortex injections of Cre-dependent AAV5-Flex-GFP and AAV5-Flex-TdTomato. All projections and collateral branches of this corticospinal hand control system throughout the neuraxis will be mapped, quantified, and rendered in 3D. The data will be uploaded to a free, publicly accessible website (https://neurodata.io/data/) for use by the research community. Aim 2: The Lesioned Primate Corticospinal Connectome How does injury affect the corticospinal connectome? How does the corticospinal system adapt to injury and alter its set of outputs, and how are these changes associated with functional recovery? We will use the elegant and novel tools of Aim 1 to map the injured and reorganized corticospinal connectome, and relate these changes to spontaneous, partial recovery of hand function after C7 hemisection lesions. This work will provide new understanding of primate anatomical and functional adaptation to injury at an unprecedented depth, and identify potential targets for enhancing functional repair. 1