Figure 9.

Enhanced acquisition and impaired retention of spatial memory by Shank1 mutants in the eight-arm radial maze task. Two of eight arms were baited to test simultaneously reference and working memory. A, Total number of reference memory errors during acquisition training (+/+, black line, n = 15; −/−, gray line, n = 14). Mice received a total of 84 trials; data are presented in blocks of four trials. B, Total number of working memory errors (revisiting errors) across training. Shank1^−/− mice make significantly fewer reference memory errors (genotype effect, F_(1,27) = 10.98; p < 0.003, repeated measures two-way ANOVA) and working memory errors (genotype effect, F_(1,27) = 10.41; p < 0.004) than wild-type mice. C, Shank1^−/− mice correctly select a baited arm with their first arm selection more frequently than wild type (genotype effect, F_(1,27) = 49.72; p < 0.0001). Data are shown in blocks of eight trials. D, Latency (time in seconds) to complete the trials in the eight-arm radial maze task is presented as means of four trials. E, Impaired spatial memory retention in Shank1^−/− mice. Mice were retested in the radial maze task 28 d after completion of initial training (white bars); data are the mean of four trials. “End-training” (black bars) shows the performance during the last four-trial block of the acquisition phase shown in A. There is no significant difference in the performance of wild-type mice, but mutants perform significantly worse after 28 d without exposure to the maze. *p < 0.02; NS, p > 0.05, t test. F, Reversal training shows enhanced behavioral plasticity in Shank1^−/− mutants. Position of baits was changed, and mice were retrained to learn new positions of baits. There was no difference in initial reversal trials (trials 1–16, genotype effect, F_(1,27) = 0.30; p = 0.59), but Shank1^−/− mice made fewer reference memory errors compared with wild type over last 20 trials (genotype effect, F_(1,27) = 7.81; p < 0.01). G, Graph comparing standard (black) and intensive training protocols (gray) in the eight-arm radial maze task. For the intensive training, wild-type and Shank1^−/− mice received a total of 60 trials over 22 training days. H, Despite intensive training, wild-type mice (n = 17) still make more reference memory errors than Shank1^−/− mice (n = 18) (genotype effect, F_(1,33) = 10.86; p < 0.003, repeated measures two-way ANOVA). Data are presented in blocks of four trials. I, Defect in memory retention in Shank1^−/− mutants after intensive training (+/+, −/−, n = 9 mice each). When tested 28 d after completion of intensive training, mutant mice make more reference memory errors compared with last four-trial acquisition block, whereas wild-type performance shows no significant deterioration. “End-training” represents last four-trial block shown in H. **p < 0.005; NS, p > 0.05, t test.