Fig. 2: iSPNs in RC LRRK2 mice have decreased excitability.
a, b Representative whole-cell current-clamp recordings of dSPNs and iSPNs in WT and RC LRRK2 KI mice. The three injection steps shown represent the currents for the different voltage responses, the hyperpolarization response, the first occurrence of action potentials, and the maximum firing, respectively. No differences in the frequency-current (F-I) function were found for dSPNs between WT and RC mice at the current where the half-maximum firing occurred in the population data (I = 475 pA, spikesWT = 12.0 ± 4.0, n = 20 cells; spikesRC = 14.0 ± 3.0, n = 30 cells; p = 0.21, Mann–Whitney U test). For iSPNs there was a decrease of the firing response to half-maximum firing current in the RC mice compared to the WT mice (I = 325 pA, spikesWT = 14.0 ± 5.0, n = 20 cells; spikesRC = 6.0 ± 6.0, n = 23 cells; p = 0.037, Mann–Whitney U test). The current where the maximal difference between the F-I functions for the WT and RC mice was also calculated (I = 625 pA, dotted line) to compare the number of elicited spikes between the WT and RC mice. We found a decrease in the number of spikes elicited in RC mice compared to WT mice (spikesWT = 22.0 ± 4.5, n = 17 cells; spikesRC = 15.0 ± 5.0, n = 23 cells; p = 0.0011, Mann–Whitney U test). c, d Representative whole-cell current-clamp recordings of dSPNs and iSPNs in WT and GS LRRK2 KI mice with population F-I data. For GS mice, no differences were found in the half-maximum firing responses for either dSPNs (spikesWT = 8.0 ± 5.0, n = 13 cells; spikesGS = 11.0 ± 3.0, n = 29 cells; p = 0.12, Mann–Whitney U test) or iSPNs (spikesWT = 10.5 ± 4.8, n = 20 cells; spikesGS = 12.0 ± 4.0, n = 28 cells; p = 0.73, Mann–Whitney U test). F-I data are shown as mean ± standard error of the mean. * denotes p < 0.05. See Supplementary Table 2 for complete sample sizes and statistical results.
