Figure 5.

No fear response to tone alone without tone-footshock association, and long-lasting cued fear memory in the kinase-dead CaMKIIα (K42R)-KI mouse. A, Fear response after repeated exposure to tone alone for three times without footshocks (3CS alone). Both wild-type (WT; left) and CaMKIIα (K42R)-KI mice (right) showed almost no freezing in the three conditions tested, demonstrating the specificity of fear response to tone-footshock association in both genotypes (Fig. 4). WT, n = 13. K42R, n = 13. B, Long-term memory examined four weeks after strong 1CS-US conditioning. The mice in Figure 4B were retested four weeks later. Left, Wild-type mice still showed context-dependent and tone-dependent freezing, demonstrating the acquired fear memory was long-lasting; n = 16. Right, CaMKIIα (K42R)-KI mice also retained tone-dependent freezing, demonstrating the acquired fear memory was long-lasting; n = 14. C, Long-term memory examined four weeks after 3CS-US conditioning. The mice in Figure 4C were retested four weeks later. Here again, both wild-type (left) and CaMKIIα (K42R)-KI mice (right) retained once acquired fear memory. WT, n = 16. K42R, n = 15. D, Long-term memory examined four weeks after 5CS-US conditioning. The mice in Figure 4D were retested four weeks later. Left, Wild-type mice still showed tone-dependent freezing, but not context-dependent freezing; n = 15. Right, CaMKIIα (K42R)-KI mice revealed tone-dependent freezing this time, indicating that cued fear memory had been acquired from the beginning after 5CS-US conditioning, but had been masked due to generalized fear when tested soon after conditioning (Fig. 4D, right). However, when generally increased fear subsided in four weeks, tone-dependent freezing became apparent; n = 14; **p < 0.01, ***p < 0.001, ****p < 0.0001, Bonferroni’s post hoc test.