Figure 4. DCC-dependent rerouting of mesolimbic dopamine axons to the mPFC improves cognitive control.

(A) Dcc^lox/+DAT^Cre mice required fewer trials than their wild-type littermates in the extradimensional (ED) part of the attentional set shifting task, indicating superior behavioral flexibility (Two-way mixed design ANOVA, genotype × task interaction, F_{(3, 72)} = 2.749, p = 0.049; no effect of genotype, F_{(1, 24)} = 0.01038, p = 0.9197; no effect of task, F_{(3, 72)} = 2.123, p = 0.1048. Significant difference between genotypes during the ED shift, Bonferroni post hoc, p <0.05. Dcc^lox/+DAT^Cre n = 14; Wild-type n = 12). (B) Diagram of the Go/No-Go task we adapted for mice. (C) Dcc^lox/+DAT^Cre mice make significantly fewer commission errors than wild-type mice. (Two-way mixed design ANOVA, main effect of genotype, F_{(1, 11)} = 7.599, p = 0.0187; main effect of time, F_{(9, 99)} = 8.783, p < 0.0001; no interaction, F_{(9, 99)} = 0.3734, p = 0.94. Dcc^lox/+DAT^Cre n = 6; Wild-type n = 7). (D) There are no differences between the genotypes on the number of ‘Hits’ (Two-way mixed design ANOVA, no effect of genotype, F_{(1, 11)} = 1.998, p = 0.185; main effect of time, F_{(9, 99)} = 2.654, p < 0.0085; no interaction, F_{(9, 99)} = 1.473, p = 0.1686. Dcc^lox/+DAT^Cre n = 6; Wild-type n = 7). (E) No differences between genotypes in spatial learning in the Morris Water Maze. (Two-way mixed design ANOVA, main effect of day, F_{(4, 64)} = 14.67, p < 0.0001; no effect of genotype, F_{(1, 16)} = 1.972, p = 0.1793; no interaction, F_{(4, 64)} = 0.7876, p = 0.5375. Dcc^lox/+DAT^Cre n = 10; Wild-type n = 8). (F) No differences in the amount of time spent in the target quadrant between genotypes during the probe test in the Morris Water Maze. (Two-way mixed design ANOVA, main effect of quadrant, F_{(3, 48)} = 12.73, p < 0.0001; no effect of genotype, F_{(1, 16)} = 0.7938, p = 0.3862; no interaction, F_{(3, 48)} = 0.2690, p = 0.8474. Dcc^lox/+DAT^Cre n = 10; Wild-type n = 8).