Transgenic mice with expanded neocortex due to human ARHGAP11B exhibit increased memory flexibility (2021)
Figure 4

Figure 4 - Enhanced memory flexibility in adult 11B mice.

IntelliCage was used to evaluate the memory flexibility of adult 11B mice. Four separate sessions were carried out: (i) 5 WT males together with 5 11B males; (ii) 5 other WT males together with 5 other 11B males; (iii) 5 WT females together with 7 11B females; (iv) 4 other WT females together with 8 other 11B females. Data are the mean of the total 10 males (WT), 10 males (11B), 9 females (WT) and 15 females (11B) adult littermate mice. Data points were obtained at consecutive days, error bars indicate SD. (A, B) Quantification of the discrimination error rate in the first 100 visits during the drinking phase of the acquisition stage of adult wildtype (WT) and 11B mice (male, A; female, B) in the IntelliCage. Overall place learning performance of WT and 11B mice was analysed using two-way ANOVA followed by Fisher's LSD test; all data points during the acquisition phase were included. For males (A), WT vs. 11B, P > 0.05; data over time, **** P < 0.0001; interaction, P > 0.05. For females (B), WT vs. 11B, P > 0.05; data over time, **** P < 0.0001; interaction, P > 0.05. (C, D) Quantification of the discrimination error rate in the first 100 visits during the drinking phase of the six reversal sessions of adult wildtype (WT) and 11B mice (male, C; female, D) in the IntelliCage. Overall reversal place learning performance and memory flexibility of WT and 11B mice were analysed using two-way ANOVA. For males (C), WT vs. 11B, ** P = 0.004358; data over time, **** P < 0.0001; interaction, P > 0.05. For females (D), WT vs. 11B, ** P = 0.000578; data over time, **** P < 0.0001; interaction, P > 0.05. Differences between WT and 11B mice at each individual training day were compared by Fisher's LSD tests following two-way ANOVA, * P < 0.05. P = 0.0037718 (C, day 10), P = 0.043855 (C, day 24); P = 0.018903 (D, day 12), P = 0.045954 (D, day 29); P = 0.041434 (D, day 330). (A-D) Note that (i) the two male sessions (pooled in panels A, C) and the two female sessions (pooled in panels B, D) yielded essentially the same results, and (ii) not shown in panels A-D, the two separate male sessions yielded essentially the same results, and the two separate female sessions yielded essentially the same results.

E, F Quantification of the time spent (E) and the time active (F) in the light side of the light dark box. Data are the mean of 12 male (WT), 1 male (11B), 9 female (WT) and 12 female (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test, * P < 0.05. P = 0. 0417 (E, male); P = 0. 0401 (F, male).

G, H Quantification of the percentage of the time spent in the center area of the open field arena (G), and quantification of the latency to enter the center area (H) of the open field arena. Data are the mean of 7 male (WT), 12 male (11B), 8 female (WT) and 9 female (11B) adult littermate mice. Error bars indicate SD, * P < 0.05. Two-tailed unpaired Student's t-test, P = 0. 0114 (G, male); Mann-Whitney test, P = 0. 0193 (H, male).

Data information: The lack of statistical significance for female WT vs. 11B mice in the light dark box test (E, F) and the open field test (G, H) presumably reflects the greater variability among females as compared to males due to non-synchronized estrus cycles.

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