Fig. 4
DA neurons in the PN of Tg2576 mice show hyperexcitability at 3 months of age. A Representative double immunofluorescent labelling for TH (blue) and biocytin-filled neuron (extravidin; red) in VTA coronal sections (scale: 100 μm). On the right are high magnification images of labelling for TH (blue) and biocytin-filled (red) recorded neurons (scale: 20 μm). B Representative AP traces, recorded in current-clamp mode following 50 pA-stepped depolarizing current injections (scale: 100 ms; 20 mV, 200 pA) in PN DA neurons from WT and Tg2576 mice initially held at − 60 mV, and plot demonstrating the average number of AP (± s.e.m.) elicited every 100 pA depolarizing steps (WT n = 16 cells; Tg2576 n = 12 cells from 10 mice each; two-way ANOVA for genotype vs injected current: interaction: F7,152 = 0.4341, p = 0.8796; genotype: F1,152 = 4.82, p = 0.0297; injected current: F7,152 = 7.197, p < 0.0001). C Sub-threshold responses to 50 pA-stepped hyperpolarizations of PN neurons (scale: 100 ms; 20 mV, 100 pA) and mean current/voltage relationship (± s.e.m.; WT: n = 16 neurons, 7 mice; Tg2576: n = 15 neurons, 9 mice). D The traces show representative responses of WT and Tg2576 neurons to short 10 pA-stepped depolarizing current injections (scale: 20 ms; 15 mV; 100 pA), scaled to show the AP threshold. The dashed lines show the threshold potential measured from the first AP elicited. The plots show the amount of injected current to generate the first AP (rheobase) and the threshold value for WT and Tg2576 neurons (WT: n = 10 neurons, 6 mice; Tg2576: n = 11 neurons, 7 mice; Rheobase: **p = 0.0039; Threshold: *p = 0.0248, both with Welch’s t-test). E Spontaneous firing recorded from PN and PBP neurons of the VTA (scale: 1 s; 0.2 mV), and respective plots showing instantaneous firing frequency (WT, PN: n = 16 neurons, 4 mice; Tg, PN: n = 28 neurons, 7 mice; WT, PBP: n = 16 neurons, 5 mice; Tg2576, PBP: n = 11 neurons, 5 mice; Welch’s t-test, *p = 0.037)