Figure 6.
Pro-aggregant TauRD mice show impaired learning in the Morris water maze (MWM) and in the passive avoidance task. MWM acquisition (A, B) and probe trial (C) are shown. A, Escape latencies indicate a slower acquisition in pro-aggregant TauRD mice (red circles) compared with control (blue triangles) and anti-aggregant (green squares) mice. B, Four months later, mice were subjected to a reversal phase in which the platform was placed in another position (right). Pro-aggregant TauRD mice that had been switched on for 10 months and then switched off for 4 months (dashed line) acquired the new position at the control level, whereas pro-aggregant TauRD mice where expression of the transgene was continued were much worse at this task (full line). C, Heat plots for the pro-aggregant TauRD mice on day 2 of the reversal acquisition are shown (dwell frequency is indicated by coloration from red through blue). Pro-aggregant TauRD mice expressing TauRD (left plot) spent more time searching in the former platform quadrant (filled circles) than in the quadrant of the new platform (open circles). After suppression of pro-aggregant TauRD (10 months ON + 4 months OFF; right plot), the mice had a clear preference for the new target quadrant. D, Mean latencies during training and test trial in the passive avoidance task. Switched-ON pro-aggregant TauRD mice were impaired in retention of the single trial task as they reentered the dark compartment much faster during the retention trial compared with anti-aggregant and control mice. E, Mean latencies during the test trial in the passive avoidance task of a second cohort of mice, where the animals were separated into six groups from the beginning of the experiment. Half of the mice received doxycycline for a period of 4 months (pro-aggregant OFF, anti-aggregant OFF, and control plus Dox), whereas the rest of the mice were allowed to continue their TauRD expression. The passive avoidance task demonstrates an impaired retention for the pro-aggregant ON mice, whereas the pro-aggregant OFF mice behave as well as wild-type and anti-aggregant ON and OFF mice. All data are means ± SEM. Asterisks in A and D indicate the significance of differences between PRO-ON versus ANTI-ON and control mice (**p < 0.01; ***p < 0.001). Asterisks in B and E indicate the significance of differences between PRO-ON versus PRO-OFF, ANTI-ON, ANTI-OFF, and control mice (**p < 0.01; ***p < 0.001). Pro-aggr., Pro-aggregant; Anti-aggr., anti-aggregant.