Figure 6

Loss of Unkempt improves reversal learning. (A) Y maze, preference for novel arm. (B) Unk^cKO mice show enhanced cognitive flexibility. The Morris water maze test was carried out by measuring the latency to find the hidden platform for six hidden sessions (H1-6) and then the location of the platform was changed to measure re-learning for another five reversal sessions (R1-5). All mice showed significant spatial learning across the hidden task (session factor F(5, 85) = 10.0, p < 0.0001), but there was no genotype effect (genotype factor F(1, 17) = 1.2, p = 0.3). In the reversal task, all mice showed significant reversal learning (session factor F(4, 68) = 6.7, p < 0.01) but there was a significant genotype effect (genotype factor F(1, 17) = 14.3, p = 0.001) with Unk^cKO mice displaying much greater cognitive flexibility than control mice. (C,D) Probe trial data showing the percentage of time spent in each quadrant after the hidden (C) and reversal (D) trials. L = left, O = opposite, R = right, T = target quadrant. Unk^cKO mice showed a significant preference for the opposite quadrant, indicating reference memory in the reversal task (t(17) =  − 3.3, p < 0.01). (E) Representative tracing of control and Unk^cKO mice in the probe trial of the Morris water maze reversal task. The platform is located in the bottom right quadrant. (F) Turn angle (degrees) made by mice during the probe trial for the reversal task was significantly increased in Unk^cKO compared to controls (t(17) = 2.6, p < 0.05). (G,H) Swim speed during hidden (G) and reversal (H) Morris water maze (MWM) probe trials. Control n = 11, Unk^cKO n = 8. Statistical significance for genotype effects for each session (genotype factor) and between the daily sessions (session factor) of the Morris water maze were calculated using two-way ANOVA. Comparisons between Unk^cKO and control mice were made using a Students t-test, *p < 0.05, **p < 0.01 compared to control. (I) A model for mTORC1 signaling in the brain.