Figure 2. Dlx5/6^+/− mice exhibit a post-adolescent onset of increased anxiety and impaired cognitive flexibility.

(A) 7 week old Dlx5/6^+/− mice and their WT littermates spend similar amounts of time in the center of an open field. In a distinct 10 week old cohort, Dlx5/6^+/− mice spend less time in the center than do WT littermates.

(B) In the elevated plus maze, 7 week old Dlx5/6^+/− mice and their WT littermates spend similar amounts of time in the open arms. In a distinct 10 week old cohort, Dlx5/6^+/− mice spend less time in the open arms than do WT littermates.

(C) Schematic illustrating the rule-shifting task, in which mice chose one of two bowls, each baited by an odor (O1 or O2) and a textured digging medium (TA or TB), to find a food reward (the stimulus associated with reward is indicated in red). Mice first learn an initial association (IA) between a stimulus (e.g., odor O1) and food reward. Once mice reach the learning criterion (8 correct out of 10 consecutive trials), this association undergoes an extra-dimensional rule shift (RS), e.g., from O1 to a texture (TA). Mice adapt to a reversed light/dark cycle, undergo food restriction, and are habituated to the bowls, textured digging media, and food rewards before beginning testing.

(D) Performance in the initial association and rule-shift is similar for 7 week old Dlx5/6^+/− and WT mice.

(E) There is no significant difference in “perseverative” errors, i.e., errors that are consistent with the initial rule, for 7 week old Dlx5/6^+/− and WT mice.

(F) Performance of adult Dlx5/6^+/− mice and their WT littermates on the initial association and rule shift.

(G) During the rule-shift, Dlx5/6^+/− mice made a preponderance of perseverative errors compared to “random errors,” i.e., errors that are inconsistent with both the old and new rules.

All data show means ± SEM and analyzed using two-tailed Student's unpaired t-tests. *p < 0.05, **p < 0.01, ***p < 0.001.

See also Figure S3.