The spinal cord houses the neuronal networks responsible for executing various motor tasks involved in locomotion. These spinal networks receive descending commands from the brain and brain stem. Spinal cord injury (SCI) disrupts the connectivity between the brain and the spinal cord locomotor networks, leading to a significant loss of motor control. Despite a dire need to develop ways to restore motor function after SCI, treatment options remain limited. We recently demonstrated that the primary somatosensory cortex (SI) could directly control the locomotor central pattern generator in the lumbar spinal cord via cervical excitatory interneurons (SI locomotor pathway), independent of the motor cortex. Based on the paradigm-shifting discovery that the sensory cortex can directly modulate spinal locomotor networks, this proposal aims to define the mechanism of this sensory cortical control of locomotion and harness this pathway to restore walking after SCI. First, in Aim 1, using a head-mounted miniature microscope, we will use circuit-specific single-cell resolution calcium imaging of SI-cervical pyramidal neurons in freely moving mice. This strategy will allow us to identify and decipher the neuronal activity patterns correlated to the initiation and speed of locomotion. Moreover, using a circuit-specific optogenetic approach, we will determine if direct and specific stimulation of this pathway is sufficient to initiate movement in health and after SCI. Aim 2 will determine this pathway's anatomical connectivity and integrity using intersectional viral tracing experiments and comprehensive mapping of SI-cervical pyramidal axon collaterals. In Aim 3, to determine the therapeutic potential of this pathway for locomotor recovery after spinal cord injury, we will employ acute optogenetic and chemogenetic strategies. Overall, understanding the functional significance of the SI-locomotor pathway and delineating the anatomical connectivity and integrity post-SCI will enhance our knowledge of this newly discovered circuitry and facilitate the development of strategies to restore movement after SCI and other neurological conditions with impaired movement.