Treadmill exercise improves motor deficits and partially normalizes electrophysiological properties of substantia nigra pars reticulata PV-lineage neurons in 6-OHDA-lesioned mice

Objective To examine whether treadmill exercise improves motor deficits and alters electrophysiological properties of substantia nigra pars reticulata (SNr) PV-lineage neurons in 6-OHDA-lesioned mice. Methods Male Pvalb-Cre;Ai14 mice were assigned to Sham, 6-OHDA-lesioned sedentary (PD), and 6-OHDA-lesioned treadmill-exercise (PD+EX) groups. A unilateral 6-OHDA lesion model was established by right striatal injection of 6-OHDA. PD+EX mice underwent treadmill training for 30 min/day, 5 days/week for 6 weeks. Motor function was assessed using a 10-min open-field test and three 300-s rotarod trials. Lesion verification, PV Western blotting, and whole-cell patch-clamp recordings of SNr PV-lineage neurons were performed. Results Six weeks of treadmill exercise partially improved open-field and rotarod performance in 6-OHDA-lesioned mice. Exercise was also accompanied by partial normalization of several electrophysiological abnormalities in lesioned-side SNr PV-lineage neurons, including input resistance, action potential threshold, evoked firing capacity, F–I gain, and firing adaptation. No significant group differences in regional PV protein abundance were observed. Conclusion Treadmill exercise improved motor performance and was accompanied by partial normalization of the electrophysiological properties of SNr PV-lineage neurons in 6-OHDA-lesioned mice.