FIGURE 4. Improved spatial learning and memory in I-1* mutant mice.

a, Spatial learning in control mice (n = 10) and mutant mice on dox (n = 10) trained on seven consecutive blocks of two trials (90 seconds each) separated by 30–60 min. b, CaMKII and GluR1 phosphorylation in spatial training. Control and mutant mice on dox were trained as in a, and the levels of pCaMKII and pGluR1 were analysed by western blotting of membrane-enriched hippocampal preparations either before training (naive, CaMKII: control (C), n = 2; mutant (M), n = 2; GluR1: C, n = 4; M, n = 3) or 10 min after 4 training blocks (CaMKII: C, n = 2; M, n = 3; GluR1: C, n = 4; M, n = 3) or 7 training blocks (CaMKII: C, n = 3; M, n = 2; GluR1: C, n = 3; M, n = 3) (top panels). Total CaMKII and GluR1, and -actin were measured for quantification. Per cent increase in CaMKII and GluR1 phosphorylation in naive mice versus trained mice after 4 and 7 training blocks (bar graphs). c, Spatial acquisition in control mice (n = 28) and mutant mice on dox (n = 27) trained on nine consecutive blocks of three trials (60 seconds each) separated by 24 h. This training phase was followed by a 7-day training period using another platform position (not shown). d–f, Spatial memory in control and mutant mice treated with dox either d, during and after training (on/on dox); e, only during training (on/off); or f, only after training (off/on) and probe trials were performed 3 h (time point 0, control, n = 28; mutant on dox, n = 28; mutant off/on dox, n = 13; mutant on/off dox, n = 6), 2 weeks (control, n = 28; mutant on dox, n = 19; mutant off/on dox, n = 13; mutant on/off dox, n = 6), 4 weeks (control, n = 28; mutant on dox, n = 16; mutant off/on dox, n = 11; mutant on/off dox, n = 6), 6 weeks (control, n = 28; mutant on dox, n = 15; mutant off/on dox, n = 13; mutant on/off dox, n = 6), and 8 weeks (control, n = 24; mutant on dox, n = 14; mutant off/on dox, n = 13; mutant on/off dox, n = 5) after training. In mutant on/off dox, behavioural testing was performed two weeks after dox removal. Dashed lines indicate chance level (25%). g, h, Spatial performance in aged mice. Learning curve (g), and probe trials (h), in aged control (n = 9) and mutant (n = 9) mice trained on nine consecutive blocks of three trials separated by 24 h (no platform transfer) and treated with dox during and after training. Probe trials were performed 1 day (time point 0), 2 weeks, 4 weeks, 6 weeks and 8 weeks after training. For all experiments, the time spent in other quadrants of the maze was similar in all groups and not significantly different from chance (not shown). Asterisk, P < 0.05; double asterisk, P < 0.01.