Figure 1

Improved behavioral flexibility and reduced excitability of layer V mPFC pyramidal neurons in dcc haploinsufficient mice. (a–c) Depolarizing current steps (30pA) were injected into layer V pyramidal neurons of the pregenual mPFC (spanning the cingulate 1 and prelimbic subregions) to estimate the rheobase current, which was defined as the first current step capable of eliciting one action potential. (a) The average injected current that was required to trigger an action potential (1st spike) was significantly higher in adult dcc haploinsufficient mice compared with wild-type littermate controls (wild-type: n=6; dcc haploinsufficient: n=8; t₍₁₂₎=3.013, P=0.0108). (b) The average action potential threshold of Layer V pyramidal neurons is significantly higher in dcc haploinsufficient mice (wild-type: n=6; dcc haploinsufficient: n=8; t₍₁₂₎=3.788, P=0.0026. (c) Representative membrane potential traces recorded from mPFC layer V pyramidal neurons of wild-type and dcc haploinsufficient mice. Note that more current steps are needed to trigger action potential formation in dcc haplosinsufficient mice. (d) dcc haploinsufficient mice exhibit increased behavioral flexibility in the Attentional Set-Shifting Task. No differences were observed between dcc haploinsufficient and wild-type mice in the mean number of trials to criterion required to solve the SD, CD, and ID tasks, indicating no differences in discrimination learning between the two genotypes (wild-type: n=8; dcc haploinsufficient: n=9; two-way repeated measures ANOVA, no significant main effect of genotype: F_(1,15)=0.285, P=0.601; no significant interaction: F_(2,30)=0.463, P=0.634). However, dcc haploinsufficient mice performed better than wild-type littermates in the ED part of the task (t₍₁₅₎=2.723, P=0.0157), indicating superior mPFC-dependent behavioral flexibility in these mice. (e) The difference in performance in the Attentional Set-Shifting Task is not attributable to genotypic differences in anxiety. There were no differences between genotypes in either the percent of entries into, or the percentage of time spent in, the open arm of the elevated plus maze, indicating that both groups displayed comparable levels of anxiety. Statistical analysis was performed on the raw data (wild-type: n=17; dcc; haploinsufficient: n=15; number of entries into open arm: t₍₃₀₎=0.081, P=0.936; time spent in open arm: t₍₃₀₎=0.214, P=0.832).