Exercise Coordinates Neural Plasticity from the Mesencephalic Locomotor Region to the Spinal Cord in Mice

Locomotion involves circuits connecting mesencephalic locomotor region (MLR) and spinal cord (SC). Although chronic exercise improves neuronal adaptability, its impact on functional and structural plasticity along the MLR–SC pathway remains unclear. Here, we examined exercise-induced neuroplasticity in MLR and lumbar SC neurons using whole-cell patch-clamp recordings from P42-P45 mice after three-week treadmill exercise. Key findings include: (1) Exercise increased excitability, shown by lowering rheobase and voltage threshold, with ventral SC neurons more affected than dorsal ones; (2) Exercise enhanced persistent inward currents (PICs) in terms of hyperpolarizing onset voltage and increasing amplitude, with effects stronger in SC than MLR neurons. Pharmacological data indicated calcium‑mediated PICs modulated firing duration/frequency, while sodium‑mediated PICs influenced threshold/capacity; (3) Exercise increased dendritic complexity (total length, branch points, and terminals), more markedly in SC versus MLR neurons; (4) Ventral spinal neurons displayed greater dendritic complexity than dorsal neurons, and were more modulated by exercise; (5) Correlation suggested exercise-driven dendritic plasticity potentiated PICs and excitability, collectively promoting locomotor adaptation. These results revealed an exercise-induced, coordinated plasticity throughout locomotor system, wherein spinal circuits, particularly ventral components, exhibited greater functional and structural adaptability than MLR. This study provided electrophysiological, ionic, and morphological insights into activity-dependent neural adaptation.