Induced Neural Activity Promotes an Oligodendroglia Regenerative Response in the Injured Spinal Cord and Improves Motor Function after Spinal Cord Injury

Myelination in the central nervous system (CNS) is a dynamic process that includes birth of oligodendrocyte progenitor cells (OPCs), their differentiation into oligodendrocytes, and ensheathment of axons. Regulation of myelination by neuronal activity has emerged as a new mechanism of CNS plasticity. Activity-dependent myelination has been shown to regulate sensory, motor, and cognitive functions. In this work, we aimed to employ this mechanism of CNS plasticity by utilizing induced neuronal activity to promote remyelination and functional recovery in a subchronic model of spinal cord injury (SCI). We used a mild contusive SCI at T10, which demyelinates surviving axons of the dorsal corticospinal tract (dCST), to investigate the effects of induced neuronal activity on oligodendrogenesis, remyelination, and motor function after SCI. Neuronal activity was induced through epidural electrodes that were implanted over the primary motor (M1) cortex. Induced neuronal activity increased the number of proliferating OPCs. Additionally, induced neuronal activity in the subchronic stages of SCI increased the number of oligodendrocytes, and enhanced myelin basic protein (MBP) expression and myelin sheath formation in dCST. The oligodendroglia regenerative response could have been mediated by axon-OPC synapses, the number of which increased after induced neuronal activity. Further, M1-induced neuronal activation promoted recovery of hindlimb motor function after SCI. Our work is a proof of principle demonstration that epidural electrical stimulation as a mode of inducing neuronal activity throughout white matter tracts of the CNS could be used to promote remyelination and functional recovery after CNS injuries and demyelination disorders.