Fig. 3. Neutral sphingomyelinase-2 (NSM) controls emotional behaviour.

Mice with a heterozygous NSM-2 knock out (fro) show reduced depression-like and anxiety-like behaviour, but preserved hedonic tone compared to wild type (WT) controls. a Novelty suppressed feeding (NSF) test. b Forced swim test (FST). c Sucrose preference test (SPT). d Elevated plus maze (EPM). e Light–dark box test (LDB, P = 0.07). f Open field test (OF). Data are expressed as means ± s.e.m. (n = 8–11 per group; *P < 0.05 vs. WT). g–i Acute inhibition of NSM with GW4869 (GW, 2 mg/kg/day, i.p.) had no effect on emotional behaviour in naïve mice (n = 7 per group; OA open arm, CA closed arm, Ctr centre). j Differences in functional connectivity of fro and WT mice. By comparing symmetric mean functional connectivity matrices (left, lower triangle: mean positive correlation coefficients of all connections within the brain; upper triangle: binarized matrix containing only the 7% strongest connections) of female fro (n = 10) and WT mice (n = 10). Significant differences (middle) were calculated using network based statistics, p > 0.193). Significant differences are displayed as 3D-networks within a transparent brain surface (right) at the respective 3D positions of the centre of gravity of each brain structure. Colour-coded nodes represent one out of 206 single brain regions (orphan nodes are not shown). Edges between the nodes represent the significantly different connections (red: fro > WT; blue: fro < WT).