Fig. 5: Clozapine induced decrease in CA1 functional connectivity is blunted in p11-KO brains.
From: A molecular mechanism mediating clozapine-enhanced sensorimotor gating

A Schematic depiction of the experimental design and selected brain regions analyzed in the fUS experiments. B Left: Heatmap showing the standardized responses of the selected brain areas in WT mice after clozapine administration (4 mg/kg). Right: Dot plot displaying the p-values of these responses on a log scale. C Correlation matrix illustrating functional connectivity differences between drug treatment and baseline in the selected brain regions of WT mice (*FDR < 0.05). D Left: Heatmap showing the standardized responses of the selected brain areas in p11-KO mice after clozapine administration (4 mg/kg). Right: Dot plot displaying the p-values of these responses on a log scale. E Correlation matrix illustrating functional connectivity differences between drug treatment and baseline in the selected brain regions of p11-KO mice (*FDR < 0.05). Left: Line graphs showing functional connectivity changes between CTX (F) or CA1 (G) and the rest of the selected brain regions over time. Right: Bar graphs showing mean functional connectivity between CTX (F) or CA1 (G) and the rest of the selected brain regions at baseline and during the last 15 min of clozapine treatment. Statistical analysis: two-way repeated-measures ANOVA, CTX (Treatment: F(1,20) = 23.49, p < 0.0001; Genotype: F(1,20) = 8.586, p = 0.0083), CA1 (Treatment: F(1,20) = 13.64, p = 0.0014; Genotype: F(1,20) = 13.69, p = 0.0014); post-hoc comparisons (Veh vs. Clz: *p < 0.05, ***p < 0.001; WT vs. p11-KO: ##p < 0.01, ###p < 0.001; Sidak’s post hoc test). H Left: Line graph showing functional connectivity changes between CA1 and CTX over time. Right: Bar graphs showing mean functional connectivity between CA1 and CTX at baseline and during the last 15 min of clozapine treatment. Statistical analysis: two-way repeated-measures ANOVA (Genotype × Treatment: F(1,20) = 4.882, p = 0.039); post hoc comparisons (Veh vs. Clz: ***p < 0.001; WT vs. p11-KO: ###p < 0.001; Sidak’s post hoc test). Sample sizes: WT mice: n = 11 (males: n = 7, females: n = 4); p11-KO mice: n = 11 (males: n = 6, females: n = 5). Data are presented as mean ± SEM. Veh vehicle, HIP hippocampal region, CA1 cornu ammonis 1, CTX cortex, fUS functional ultrasound, pfUS pharmacological functional ultrasound, fc functional connectivity, Clz clozapine, Dex dexmedetomine.