Fig. 3

DA sensitivity and intracellular [Ca2+] are altered in 4-month-old Syn DA neurons. a Extracellular recordings in SNpc DA neurons from 4-month-old rats and response to 2 min application of 30 µM DA (scale: 1 min, 0.2 mV). Expanded traces (scale: 1 s) show firing in control condition and during DA. The plot shows the firing reduction (% of control) after DA (23 cells from 8 WT, 34 cells from 10 Syn; Mann–Whitney test ***P < 1.00 × 10−4). b DA currents (30 μM, 2 min) during voltage clamp (−60 mV; scale: 2 min, 20 pA) and mean (±s.e.m.) dose–response curves (18 cells from 8 WT, 18 cells from 7 Syn; two-way ANOVA: genotype × concentration, F3,29 = 0.66, P = 0.586; concentration, F3,29 = 6.68, P = 0.001; genotype, F1,29 = 8.63, P = 0.006; WT vs Syn: 1 µM, P > 0.999, 3 µM P = 0.175, 10 µM, **P = 0.007, 30 µM *P = 0.012 with Bonferroni’s). c Baclofen-mediated currents (10 µM, 3 min; −60 mV; scale: 2 min, 50 pA), and mean (±s.e.m.) current amplitude (11 WT cells, 13 Syn cells, 3 rats each; two-way ANOVA: genotype × concentration, F1,20 = 4.78, P = 0.041; concentration, F1,20 = 23.96, P < 1.00 × 10−4; genotype, F1,20 = 16.04, P = 7.00 × 10−4. WT vs Syn: 1 µM, P = 0.337, 10 µM, **P = 0.001 with Bonferroni’s). d Infrared videomicroscopy of a patched DA neuron and a Fura-2 ratiometric image (scale: 10 μm) showing variations in cytosolic [Ca2+]. The plot shows cytoplasmic [Ca2+] in DA neurons at −60 mV (23 WT, 26 Syn cells, 7 rats each; ***P < 1.00 × 10−4, Welch’s t-test). e Somatic Ca2+ at −60 mV in control conditions and in the presence of Ca2+-free bath solution (scale: 2 min). The plot shows the level of [Ca2+] reduction (11 WT neurons from 4 rats, 11 Syn neurons from 5 rats; P = 0.338 with Welch’s t-test). f [Ca2+] levels in DA neurons from slices incubated with isradipine (200 nM, 1 h; 10 WT, 6 Syn neurons, 3 rats each; ***P = 1.00 × 10−4 with Welch’s t-test. g Transient rise in fluorescence ratio following CPA application (10 µM; scale: 2 min) and plot showing smaller CPA-induced Ca2+ increase in Syn DA neurons (5 WT, 9 Syn neurons, 3 rats each; ***P = 0.001 with Mann–Whitney test). Source data are provided as a Source Data file