ObjectiveThe aim of this study is to investigate whether treadmill exercise alleviates motor dysfunction in a mouse model of Parkinson’s disease (PD) by modulating the excitability of striatal medium spiny neurons expressing dopamine type 2 receptors (D2-MSNs).MethodsA unilateral 6-hydroxydopamine (6-OHDA) injection was performed in the right striatum of D2-Cre mice to establish a hemi-lesioned PD model, with sham-operated mice serving as controls. PD mice were subjected to treadmill exercise (1