Fig. 2.
Adult RCF mice show altered Rm, Ihand evoked AP firing in DA neurons of iVTAA, Membrane resistance (Rm) of DA neurons in the iVTA from adult RCF mice (P60) is significantly reduced compared to Controls: CTRL 287 ± 15 MΩ and RCF 237 ± 15 MΩ (n = 28 and 19, respectively; Student's t-test, t = 2.38, df = 43.86, *p < 0.05). B, Similar membrane capacitance across conditions: CTRL 60 ± 3 pF and RCF 53 ± 3 pF (28 and 19 neurons, respectively; t = 1.63, df = 42.16, p = 0.11). C, Similar AP spontaneous firing frequency between Control and RCF mice: CTRL 2.5 ± 0.4 Hz and RCF 2.1 ± 0.3 Hz (13 and 19 cells, respectively; t = 0.62, df = 22.02, p = 0.54; inset: typical cell-attached recordings). Scale bars: upper 30 pA, 1 s; lower 5 pA, 1 s. D, to the left: I–V curves depicting significant reduction of Ih amplitude in VTA DA neurons from RCF mice. In details, the two-way repeated measure ANOVA analysis returned: for ‘in vivo treatment’ (RCF vs CTR) F(1,15) = 10.49, **p = 0.0055; for membrane potential (VH), F(3,13) = 73.49, ***p = 2.08 × 10−8; and for the interaction treatment x membrane potential F(3,13) = 3.016, *p = 0.0489. The Bonferroni's post-hoc analysis returned: at VH – 60 mV, CTRL – 6.8 ± 0.7 pA, RCF – 6 ± 1 pA, p = 1; at VH – 80 mV, CTRL – 69 ± 9 pA, RCF – 42 ± 5 pA, p = 1; at VH – 100 mV, CTRL – 168 ± 17 pA, RCF – 104 ± 9 pA, **p = 0.0015; at VH – 120 mV, CTRL – 233 ± 20 pA, RCF – 165 ± 14 pA, ***p = 4.85 × 10−4 (CTRL, n = 16; RCF, n = 27). To the right, example Ih current traces (four superimposed consecutive sweeps). Scale bars: 200 pA, 0.5 s. E, frequency – injected current amplitude (f – I) average relationship (left) for evoked APs in adult CTRL or RCF neurons depicting significantly reduced ability to elicit APs in RCF mice. In details: for in vivo treatment F(1,8) = 6.49, *p = 0.034; interaction treatment x injected current F(3,6) = 3.96, p = 0.071; for injected current F(3,6) = 46.51, ***p = 1.5 × 10−4 (two-way repeated measure ANOVA). The Bonferroni's post-hoc analysis returned: with Iinj +50 pA: CTRL 3 ± 1 Hz, RCF, 1.8 ± 0.6 Hz, p = 1; Iinj +100 pA: CTRL, 8 ± 2 Hz and RCF, 4.6 ± 0.7 Hz, p = 0.77; Iinj +150 pA: CTRL, 11 ± 2 Hz and RCF, 6.6 ± 0.7 Hz, *p < 0.05; Iinj +200 pA, CTRL, 13 ± 2 Hz and RCF, 8.2 ± 0.6 Hz, *p < 0.05. To the right, typical current-clamp recordings showing evoked firing. Scale bars: 30 mV, 1 s.