Figure 1.
ERK5 icKO mice display normal shock sensitivity, acquisition and retrieval of contextual fear memory, yet show reduced contextual fear memory 6 d after training with the 3 × 0.3 mA foot shock paradigm.
A) Schematic depiction of the experimental design. B) Freezing behavior displayed by ERK5 icKO and control mice immediately following each of the 3 successive 0.3 mA foot shocks during training. C) ERK5 icKO mice have acquired and can retrieve contextual fear memory 2 min after training. D) ERK5 icKO mice show reduced contextual fear memory 6 d after training while freezing behavior in the novel context was unaffected.
Figure 2.
ERK5 icKO mice are impaired in remote memory when the erk5 gene was inducibly deleted prior to training.
A) Schematic depiction of the experimental design. Mice were treated with tamoxifen to delete erk5 before contextual fear conditioning with the 1×0.7 mA foot shock paradigm. B) Freezing behavior in the shocking context 1 d after training does not differ between ERK5 icKO and control mice. C) Remote contextual memory is impaired in ERK5 icKO mice when tested 5 wks post-training. D) Minimal freezing behavior is observed in a novel context at both 1 d and 5 wks post-training for all treatment groups. E) Amygdala-dependent, cued-fear conditioning is normal in ERK5 icKO mice at both 1 d and 5 wks post training.
Figure 3.
Deletion of the erk5 gene 6 days after training causes decay of remote contextual fear memory.
A) Schematic depiction of the experimental design. B–D) Assessment of memory formation for contextual fear conditioning (B), novel context (C), and cued fear (D) before erk5 deletion. Mice were trained with the 1×0.7 mA foot shock paradigm and freezing behavior was assessed 1 d after training. E–G) Six days after training, mice were treated with tamoxifen for 7 d to delete erk5 or with vehicle control. Freezing behavior was assessed in the training context (E), a novel context (F), or in a novel context paired with the cue (G) at 5, 9, 12, and 16 wks after training.
Table 1.
Animal genotypes and treatment.
Figure 4.
Deletion of the erk5 gene 5 weeks post-training impairs remote memory.
A) Schematic depiction of the experimental design. B–D) Assessment of memory formation for contextual fear conditioning (B), novel context (C), and cued fear (D) before erk5 deletion as in Figure 3. E–G) Five weeks after training, mice were treated with tamoxifen for 7 d to delete erk5 or with vehicle control. Remote memory for the shocking context was significantly reduced 15 wks after training in ERK5 icKO mice (E), while their response to a novel context (F) or the cue (G) was unaffected.