(A) CBP{HAT‒} mutant mice exhibit a severe impairment in recognition memory. Three groups were tested on the VPC task at 30 min and 24 hr delays: CBP{HAT‒}/Tg-ON (n = 12) that had expressed the transgene for 18 days before the assay, CBP{HAT‒}/Tg-OFF (n = 11) with blocked transgene expression, and wt (n = 13). CBP{HAT‒}/Tg-ON mice exhibited normal acquisition, short-term memory, and recall when tested on the VPC task at the 30 min delay. However, CBP{HAT‒}/Tg-ON mice were severely impaired on the VPC task at the 24 hr delay (*p < 0.05). We found no effect of Dox treatment in wild-type mice and therefore combined the data for wild-type ON/OFF Dox. t test for the % preference for novel object after 30 min delay: wt/OFF-Dox versus wt/ON-Dox, p > 0.85; wt/OFF-Dox, average = 86%, n = 7, SEM ± 0.8; wt/ON-Dox, average = 88%, n = 6, SEM ± 0.5. t test for the % preference for novel object after 24 hr delay: wt/OFF-Dox versus wt/ON-Dox, p > 0.89; wt/OFF-Dox, average = 79%, n = 7, SEM ± 0.8; wt/ON-Dox, average = 81%, n = 6, SEM ± 0.8.
(B) The performance of CBP{HAT‒}/Tg-ON and wt mice was tested on the VPC task at the 24 hr delay after CBP{HAT‒} transgene expression was activated for 2, 4, or 5 days before training. Expression of the CBP{HAT‒} transgene for 2 days before training was sufficient to block long-term memory formation assessed at the 24 hr delay. Both groups of animals, CBP{HAT‒}/Tg-ON and control wt littermates, received exactly the same Dox treatment before and during the experiment.
(C) Performance on the MWM task during training on Protocol 1 (see Experimental Procedures). CBP{HAT‒}/Tg-ON mice were trained together with two control groups: CBP{HAT‒}/Tg-OFF and wt mice for 12 days (2 trials/day, 1 hr ITI). No differences in escape latencies were found between CBP{HAT‒}/Tg-ON mice and two control groups.
(D) CBP{HAT‒}/Tg-ON mice show a deficiency in spatial memory on the MWM task. A probe trial performed 1 day after training was complete revealed a significant impairment in spatial localization in the CBP{HAT‒}/Tg-ON group compared to controls (t test for time in target quadrant: *CBP{HAT‒}/Tg-ON versus wt, p < 0.02; CBP{HAT‒}/Tg-ON versus CBP{HAT‒}/Tg-OFF, p < 0.05). We found no effect of Dox treatment in wild-type mice and therefore combined the data for wild-type ON/OFF Dox. t test for the time in target quadrant: wt/OFF-Dox versus wt/ ON-Dox, p > 0.9; wt/OFF-Dox: average = 43.2%, n = 7, SEM ± 4.8; wt/ON-Dox, average = 44.1%, n = 5, SEM ± 6.7.
(E) CBP{HAT‒}/Tg-ON mice showed normal acquisition on the visual platform version of the MWM task indicating normal vision, motivation, and swimming ability.
The design of the experiments in this figure (except B) includes two types of animals (wild-types and double transgenics) and two treatment groups (Dox or no Dox). We performed the behavioral analysis on these four groups. However, we found no effect of Dox treatment in wildtype mice and therefore combined the data for wild-type ON/OFF Dox.