S1/2^-/- mice display novelty induced hyperactivity, decreased anxiety and exploratory behavior and working memory disturbances.

Abstract

<p>A–C) Open field test performed in a novel, unfamiliar test arena. WT: n = 24, S1/2^-/-: n = 26. A) Novelty-induced hyperactivity in S1/2^-/- mice as assessed by moving distance in the open field (p_MW = 0.0006). B) Analysis in 1 min bins yielded a significant E_genotype (F_(1,48) = 16.46; p = 0.0002). Moreover, Bonferroni posttest revealed the strongest difference between the genotypes in interval 3, 5 and 10 (p_Bonf<0.01, p_Bonf<0.05 and p_Bonf<0.05, respectively). C) Mutants spent more time in the center (p_MW = 0.0004) of the test arena indicating reduced anxiety when compared to controls. D-E) Hole board test performed with a subsequent modification of the open field setup by floor insert with holes. WT: n = 24, S1/2^-/-: n = 26. D) S1/2^-/- mice displayed no alterations in the overall activity measured as total distance travelled. E) S1/2^-/- mice performed less nose pokes into holes (p_MW = 0.0014) indicating decreased curiosity-related behavior compared to WT. F-G) Y-maze test. WT: n = 23, S1/2^-/-: n = 20. F) S1/2^-/- mice showed increased activity in Y-maze test (E_genotype F_(1,41) = 10.98; p = 0.0019) most evident in interval 0-5 min (p_Bonf<0.01). G) Mutant mice performed less alterations in Y-maze than control animals (E_genotype F_(1,41) = 4.86; p = 0.0331) and p_Bonf<0.05 for interval 5–10 min. H-J) S1/2^-/- mice display impairment of working memory in the radial arm water maze (RAWM). WT: n = 29, S1/2^-/-: n = 28. H) In the visible platform task, performance was similar in both genotypes (E_genotype F_(1,55) = 0.65; p = 0.4236). I-J) S1/2^-/- mice showed increased number of working errors searching for a hidden platform on the first (I) (E_genotype F_(1,55) = 3.93; p = 0.0524; I_{genotype×time} F_(3,165) = 2.68; p = 0.0486) and the second (J) day of experiment (E_genotype F_(1,55) = 9.05; p = 0.0044) and I_{genotype×time} F_(5,275) = 2.34; p = 0.0422). Bonferroni posttest revealed significant difference during the 3^rd trial of the second day (p_Bonf<0.001). WT, black bars/circles. S1/2^-/-, white bars/circles. Data were analyzed with 2-way ANOVA with Bonferroni posttest (p_Bonf) and Mann-Whitney test (p_MW) for pairwise comparisons. ***: p<0.001; **: p<0.01; *: p<0.05. E, effect; I, interaction of factors.</p