Fig. 4: Concomitant presence of oxidative stress and hypofunction of T-Ca²⁺ channels in TRN of a neurodevelopmental mouse model relevant to psychosis (MAM mice).

MAM mice are offspring from mothers who received a single injection of methylazoxymethanol acetate at gestational day 16. A Micrographs showing immunofluorescent labeling for 8-oxo-dG (oxidative stress marker, green), parvalbumin (PV, red), and WFA/PNN (blue) in the TRN of PND40 control and MAM mice. WFA/PNN: perineuronal net labeled with Wisteria floribunda agglutinin (WFA). Increased 8-oxo-dG labeling (B), decreased number of PV-IR neurons (C), and PNN + PV-IR neurons (D) in TRN of MAM compared to control mice. Data are from 4 mice per group. Threshold for the initial membrane potential of TRN neurons required to induce single (E), or repetitive bursting (F), upon depolarization. Note a trend for a more hyperpolarized membrane potential in order to induce bursting activity in TRN neurons of young (PND21-30) MAM (n = 13) as compared to control WT (n = 11) mice. G Density of T-Ca²⁺ currents activated at resting membrane potential (RMP) not significantly different in TRN neurons of MAM (n = 12) and control WT mice (n = 24). Density of T-Ca²⁺ (H) and SK (I) currents activated from each of the initial membrane potentials. Compared to control mice, TRN neurons in MAM mice exhibit overall significantly smaller T-Ca²⁺ (F = 73.63 DFn = 1 DFd = 578; p < 0.0001) and SK current densities (F = 61.58 DFn = 1 DFd = 544; p < 0.0001). J Correlation between T-Ca²⁺ and SK current densities (Spearman r = −0.96 for WT and −0.99 for MAM; p < 0.0001 for both groups). Unpaired t-tests and two-way ANOVAs with Bonferroni post-tests; *p < 0.05 **p < 0.01 ***p < 0.001. Data are presented as means ± s.e.m.