Figure 2. Inhaling CO₂ during a retrieval tone augments the effect of reconditioning.

(A) Schematic of protocol for memory enhancement. During aversive conditioning, mice received 3 paired tones and foot shocks in context X. The Ret/CO₂ period in context Y was as described for Figure 1A. Thirty minutes later, mice received a tone paired with a foot shock in context Z as reconditioning (Re-Cond.). Memories were tested 1 day later by presenting 4 tones in context ZZ. See also Figure 1—source data 1 and Figure 2—figure supplements 1 and 2. (B,C) Percentage of time freezing during aversive conditioning (B) and the memory testing (C) in wild-type (WT) mice. Data are mean±SEM. n = 16 mice in each group. * indicates p<0.05 by ANOVA with Tukey’s post hoc multiple comparison. No ret vs Ret, p=0.0295; No ret vs No ret + CO₂, p=0.7774; No ret vs Ret + CO₂, p<0.0001; Ret vs No ret + CO₂, p=0.1763; Ret vs Ret + CO₂, p=0.0055; No ret + CO₂ vs Ret + CO₂, p<0.0001. (D,E) Data as in panels B and C except in Asic1a^−/− mice. Data are mean±SEM. n = 16 mice in each group. * indicates p<0.05 by ANOVA with Tukey’s post hoc multiple comparison. ‘ns’ indicates not statistically significant. No ret vs Ret, p=0.0055; No ret vs No ret + CO₂, p=0.6228; No ret vs Ret + CO₂, p=0.0006; Ret vs No ret + CO₂, p=0.1242; Ret vs Ret + CO₂, p=0.9049; No ret + CO₂ vs Ret + CO₂, p=0.0248.

DOI: http://dx.doi.org/10.7554/eLife.22564.006

Figure 2—figure supplement 1. Distinct contexts were used to test the effect of retrieval on memory enhancement.

(A) Schematic of protocol for auditory aversive conditioning, memory modification, and testing. The protocol was identical to that shown in Figure 2A. (B) Data are the percentage of time mice were freezing in the four different contexts before aversive conditioning, before the retrieval tone, before reconditioning, and before the memory test. Data are mean ±SEM. n = 16 mice in each group. There were no statistically significant differences between groups by ANOVA with Tukey’s post hoc multiple comparison.

DOI: http://dx.doi.org/10.7554/eLife.22564.007

Figure 2—figure supplement 2. Reconditioning enhances an aversive memory.

(A) Schematic of protocol for auditory aversive conditioning, memory modification, and testing. The protocol was identical to that shown in Figure 2A. (B–E) Data are percentage of time mice were freezing in response to tones during the indicated components of the protocol. Data are mean ±SEM. n = 8 mice in each group. * indicates p<0.05 by unpaired Student’s t-test. No re-cond. vs Re-cond., p=0.0410.

DOI: http://dx.doi.org/10.7554/eLife.22564.008