Figure 5. Prenatal ERK inhibitor treatment partially rescues ventral hippocampal and lateral septal volume in 16p11.2del mice. Mice were treated for 5 consecutive days starting at E10.5 and evaluated at P90. A, TBM analyses revealed significant increased volume of SC, PAG and Hypo in 16p11.2del mice compared with WT littermates (t test, p < 0.01 FWE cluster-corrected, with cluster defining threshold of |t| > 2.3). In 16p11.2 deletion mice, we also observed an increased volume of the RS ctx, as well as reduced volume of vHPC, LS, Ent ctx, and Amy (t test, p < 0.01 FWE cluster-corrected, with cluster defining threshold of |t| > 2.3). b, Comparison between treated and nontreated 16p11.2del mice shows that ERK-inhibitor produces bilateral foci of increased volume in the vHPC and LS (t test, p < 0.01 FWE cluster-corrected, with cluster defining threshold of |t| > 2.3). c, A composite illustration of a and b revealed that foci of increased gray matter volume (red/yellow; from b) are spatially located in the same hippocampal and septal regions exhibiting reduced gray matter volume in 16p11.2 del mice (blue/light blue; from a), suggesting a partial anatomical rescue of volumetric deficits upon treatment with ERK inhibitor. d, e, Consistent with TBM results, anatomical labeling revealed reduced relative volume in vHPC (t test: t(17) = 3.78, p = 0.001) and LS (t test: t(17) = 2.21, p = 0.041) in 16p11.2del mice compared with WT littermates (one-way ANOVA of vHPC: F(3,34) = 8.083, p < 0.001; one-way ANOVA of LS: F(3,34) = 1.692, p = 0.1872). Treatment with ERK inhibitor in 16p11.2del mice partially restored morphoanatomical volume in these brain regions (vHPC, t test: t(16) = 2.79, p = 0.013), although the effects in LS did not reach full statistical significance (t test, t(16) = 1.78, p = 0.078). Amy, Amygdala; Ent ctx, entorhinal cortex; Hypo, hypothalamus; LS, lateral septum; PAG, periaqueductal gray; RS, retrosplenial cortex; SC, superior colliculus; vHPC, ventral hippocampus. *p < 0.05,**p < 0.01.