Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways

108Chronic primary motor cortex (M1) electrical stimulation upregulates mTOR and Jak/Stat pathway signaling in corticospinal tract (CST) neurons. This, in turn, promotes CST axonal outgrowth and presynaptic site formation in the ipsilateral spinal cord gray matter. Without stimulation (top), mTOR and the Jak/Stat signaling in M1 are weak (blue) and ipsilateral CST axon and synapse density are both low (blue-yellow). After 10 days of daily stimulation, mTOR and Jak/Stat signaling in M1 is strongly upregulated (yellow-red) and CST axonal projections and presynaptic sites become denser (red).