(A) DA lesion and chronic L-DOPA treatment paradigm. 3–4 weeks after unilateral 6-OHDA lesion, mice were randomly divided into two groups to receive either saline or L-DOPA. Experimental groups included sham: mice with vehicle injection into the MFB, 6-OHDA: mice with MFB lesions injected with daily IP saline, and chronic LD: MFB-lesioned mice treated with 3 mg/kg L-DOPA IP once daily. Electrophysiological slice recordings were carried out 3–11 weeks after the initiation of L-DOPA or saline injections. (B) Representative cell-attached recordings and distributions of average (per cell) instantaneous spontaneous action potential frequency (sAP) of ChIs from sham-lesioned (n = 83 neurons/26 mice), 6-OHDA-lesioned (n = 81 neurons/29 mice), and 6-OHDA-lesioned mice treated with chronic LD (n = 87 neurons/25 mice). Scale bars are 1 s and 50 pA. (C) Dot plots of spontaneous cell activity in the absence (same as in B) and the presence of synaptic blockers CNQX (10 µM), APV (25 µM) and picrotoxin (PCX) (25 µM). Number of recordings with synaptic blockers: sham n = 13 neurons/3 mice, 6-OHDA n = 11 neurons/3 mice, chronic-LD 13 neurons/3 mice. (D) Coefficient of variation (CV) of instantaneous sAP frequencies in sham, 6-OHDA, and chronic LD groups (same N as in B). For C and D, line denotes median, error bars show interquartile range, p<0.05 (*), p<0.01 (**), p<0.001 (***), or p<0.0001 (****) by Kruskal-Wallis test with Dunn’s multiple comparison test; (E) The number of evoked action potentials following current injection was decreased in ChIs from 6-OHDA lesioned mice but restored to sham levels after chronic L-DOPA treatment. p<0.01 (**), 6-OHDA vs. the two other groups by two-way ANOVA with Tukey’s post-hoc test; sham n = 11 neurons/4 mice, 6-OHDA n = 16 neurons/5 mice, chronic-LD n = 18 neurons/5 mice. (F) Averaged perforated-patch recordings of sAP in ChIs following 30 µM DA perfusion in the presence of synaptic blockers. Sham n = 7 neurons/3 mice, 6-OHDA n = 7 neurons/2 mice, chronic-LD n = 10 neurons/3 mice. (G) Changes in average sAP frequencies in individual cells before and after DA exposure. (same N as in F). p<0.01 (**) by paired t-test.