Figure 7.

ERK5 icKO mice exhibit reduced contextual fear memory when animals were trained with weaker electric footshocks. A, Schematic illustration of the modified cued-contextual fear-conditioning paradigm using 0.3 mA shock intensity delivered up to three times. B, C57BL/6 mice were subjected to one, two, or three footshocks (0.3 mA, 2 s each), with 2 min intershock intervals to generate a dose-dependent fear-conditioning response. Freezing behavior in the same context but without footshock was recorded 24 h later. For subsequent experiments in C–E, animals were subjected to three footshocks (0.3 mA, 2 s each), with 2 min intershock intervals. C, When placed into the same shocking context 24 h later, contextual fear memory was reduced in ERK5 icKO mice. D, The fear memory was context specific because animals did not freeze when placed into a novel context 24 h after training. E, Memory for the hippocampus-independent, auditory-cued fear conditioning measured 24 h after training was unaffected in ERK5 icKO mice. Data are mean ± SEM from two independent experiments with n ≥ 6 per treatment group per experiment. **p < 0.01.