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.