Fig. 3: Prmt9 cKO mice show impaired learning and memory.

a Graphic illustration of Morris Water Maze test, with prominent ambient visual cues surrounding the test arena to facilitate associative learning. b Prmt9 cKO mice showed slower learning during the acquisition period. The y-axis shows the time taken to find the hidden platform during the eight training days. Data are presented as mean ± SEM. Main effect on groups, F (1,12) = 19.4, p = 0.0009. *p = 0.019, **p = 0.009, ***p < 0.001. Repeated measures two-way-ANOVA with Sidak’s multiple comparison test. c Representative mouse moving tracks and speed on Day 8 of training. Heatmap, time spent at location of arena; line graph, moving trajectory of mice. Marker color denotes swimming speed at the corresponding location. d Quantification of percent time spent in each quadrant during Day 8 of training. Prmt9 cKO mice spent significantly less time (p < 0.0001, unpaired t test) in the target quadrant (TQ). Data are presented as mean ± SEM. e Prmt9 cKO mice showed impaired memory. Prmt9 cKO mice spent significantly less time in the target quadrant during the probe trial (p = 0.0013, unpaired t test). Data are presented as mean ± SEM. f Prmt9 cKO mice showed slower learning of the new platform location during Day 10–12 reverse learning period. Data are presented as mean ± SEM. p = 0.008 for the effect of genotype, repeated measures two-way rmANOVA. g Prmt9 cKO mice spent less time in the new target quadrant during the Day 11 of the probe trial (p < 0.0001, unpaired t test). Data are presented as mean ± SEM. Two-way rmANOVA with Sidak’s MCT. For (a–g), WT, n = 6 (4M2F); cKO, n = 6 (3M3F). h Schematic diagram of a Pavlovian fear conditioning paradigm. A different cohort of mice was used. WT, n = 6 (3M3F); cKO, n = 6 (2M4F). Day 1 had five training sessions in which a mild foot shock (US) was paired with an auditory cue (CS). On day 2, mice were placed in the same context with no US or CS stimulus presented. Freezing time was measured. i Prmt9 cKO mice showed decreased fear conditioning learning. Prmt9 cKO mice exhibited a significantly decreased freezing time and different time course in associating the unconditional (audio cue) stimulus with foot shock and freezing behavior compared with controls, p = 0.04, for the effects of genotype, repeated measures two-way ANOVA. Data are presented as mean ± SEM. j Prmt9 cKO mice show reduced contextual-induced freezing behavior (p = 0.005, unpaired t test). Data are presented as mean ± SEM. For (h–j), WT, n = 6 (3M3F); cKO, n = 6 (2M4F).