Altered anxiety-like behavior and modestly increased locomotor activity in Tbr1+/K228E mice. (A) Enhanced anxiety-like behavior in Tbr1+/K228E mice (3 months; male) in the elevated plus-maze test, as shown by time (total and %) spent in open/closed arms. n = 10 mice for WT and HT, *P < 0.05, **P < 0.01, two-way ANOVA with Sidak’s multiple comparison test (total time) and Mann–Whitney test (% time). (B) Enhanced anxiety-like behavior in Tbr1+/K228E mice (3 months; male) in the light-dark test, as shown by time spent in the light chamber. n = 10 mice for WT and HT, *P < 0.05, Mann–Whitney test. (C) Normal locomotor activity but decreased habituation in Tbr1+/K228E mice (3 months; male) in the open-field test. Note that the time spent in the center region of the open-field arena is abnormally increased, indicative of anxiolytic-like behavior, although the suppressed habitation to the environment, indicated by the increasing difference in the distance moved across the 10-min sections and the distance moved during the first and last 10 mins, might complicate this interpretation. n = 10 mice for WT and HT, *P < 0.05, **P < 0.01, ***P < 0.001, ns: not significant, repeated measures two-way ANOVA with Dunnett’s multiple comparisons test (Distance moved over 60 min, Center time over 60 min), Wilcoxon matched-pairs signed-rank test (10 min vs. 60 min), Student’s t-test (total distance moved), and Mann–Whitney test (total time in center). (D) Modestly increased locomotor activity in Tbr1+/K228E mice (3 months; male) in Laboras cages. Note that hyperactivity is mainly observed during the first ~6 h of the light-off period on day 1. n = 7 mice for WT and HT, *P < 0.05, **P < 0.01, ***P < 0.001, ns: not significant, two-way repeated-measures ANOVA with Sidak’s multiple comparisons test and Mann–Whitney test (light-on/off).