Figure 1. Impaired behavioral flexibility in TCDD-exposed mice (inter-session analysis).

(A) Overview of IntelliCage apparatus. (B) Group composition of mice housed and tested in each IntelliCage apparatus. (C) Behavioral sequencing task. Mice were allowed to obtain water reward for 4 seconds when they visited an “active” rewarded corner (blue circle). The location of the active rewarded corner was alternately switched between the two diagonally positioned corners each time the mouse received a reward. Thus, the mice had to acquire the behavioral sequence of alternating between the two rewarded corners to continuously obtain rewards. A visit to the never-rewarded corners (gray circles with a diagonal line) was counted as a discrimination error. (D) Serial reversal task. For each mouse, the assigned spatial patterns of the rewarded corners (seq. 1 or seq. 2) were reversed 11 times every 7 or 4 sessions. (E) Time-line of the experiment for each day. (F, G) Learning performance on the behavioral flexibility test. For the purpose of readability, data from the TC-0.6 and TC-3.0 groups of mice were separately plotted in F and G, respectively, whereas the data from the Control group are shown in F and G. Discrimination error rates (the number of discrimination errors in the first 100 corner visits in the session) are indicated as the means ± S.E.M. (n = 8/group). For each session, the individual mouse's discrimination error rate was transformed into a z-score calculated among all the mice. The bars in the insets in F and G indicate the averaged z-scores for each group in the first sessions of all the Revs (early stage of reversal learning) and in the second to fourth sessions of all Revs (late stage of reversal learning). * indicates a significant difference from the Control group (P<0.05, ANOVA followed by Tukey's post hoc test).