Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism - PubMed (original) (raw)

Figure 5

patDp/+ Mice Show Behavioral Inflexibility in the Morris Water Maze and Barnes Maze Tests (A–F) Morris water maze test; n = 20 for both genotypes. White bar, WT; black bar, patDp/+. (A) The configuration of the four quadrants in the probe test after the original training (TA, target quadrant; OP, opposite quadrant; AR, adjacent right quadrant; AL, adjacent left quadrant). (B and C) Probe test after the original training. Upper panels indicate averaged swimming traces of the swim pattern for WT (B) and patDp/+ (C) mice. Warmer color represents more time spent. Lower panels show the quadrant occupancy for WT (B) and patDp/+ (C) mice. Both WT and patDp/+ mice showed significantly more time spent in the target quadrant compared with the other quadrants [WT, F(3,76) = 12.86, p < 0.0001; _patDp/+_, _F_(3,76) = 13.31, p < 0.0001; Newman-Keuls post hoc comparison (trained quadrant more than all the other quadrants); p < 0.01 for both genotypes]. (D) The configuration of the four quadrants in the reversal probe test. (E and F) Reversal probe test. Upper panels indicate averaged swimming traces of the swim pattern for WT (E) and _patDp/+_ (F) mice. Lower panels show the quadrant occupancy for WT (E) and _patDp/+_ (F) mice. While WT mice spent significantly more time in the reversed target quadrant, _patDp/+_ mice showed no significant difference in the time spent between the quadrants [WT, _F_(3,76) = 8.20, p < 0.0001; _patDp/+_, _F_(3,76) = 2.40, p = 0.0745; Neuman-Keuls post hoc comparison (trained quadrant more than all the other quadrants); WT, p < 0.01; _patDp/+_, p > 0.05]. (G–L) Barnes maze test, n = 22 for both genotypes. White bar, WT; black bar, patDp/+. (G) The target position in the Barnes maze original probe test. The hole at 0 degrees is the correct hole chosen as the target. (H and I) Both genotypes could learn the target position spatially in the original probe test [WT, F(11,252) = 25.47, p < 0.0001; _patDp/+_, _F_(11,252) = 32.27, p < 0.0001; Bonferroni post hoc comparison (time spent around the target position more than those of all the other holes), both genotypes, p < 0.01]. (J) The target position in the Barnes maze reversal probe test. The target at 0 degrees is moved to the opposite position. The original target position is labeled in red, at 180 degrees, and the new target position is labeled in blue, at 0 degrees. (K and L) While WT mice could learn the new target position flexibly, _patDp/+_ mice could not respond as flexibly as WT mice [WT, _F_(11,252) = 29,08, p < 0.0001; _patDp/+_, _F_(11,252) = 16.04, p < 0.0001; Bonferroni post hoc comparison (target versus 180 degrees), WT, p < 0.01; patDp/+, p > 0.05]. ∗p < 0.01; n.s., not significant (p > 0.05). Furthermore, time spent around the 180 degree position and its neighboring 150 degree position was increased in patDp/+ mice compared to the WT (180 degrees, p < 0.1; 150 degrees, p < 0.05). For (B), (C), (E), (F), (H), (I), (K), and (L), error bars represent the SEM.