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. Author manuscript; available in PMC: 2020 Nov 4.
Published in final edited form as: Nat Neurosci. 2020 May 4;23(6):718–729. doi: 10.1038/s41593-020-0627-5

Figure 2. Adar1 knockdown impairs memory updating following extinction training.

Figure 2.

a, Schematic of the behavioral protocol used to test the effect of lentiviral-mediated knockdown of Adar1 in the PFC on fear extinction memory. CTX, context; CS, conditioned stimulus; 3CS, a test with three conditioned stimuli; CS1, the first conditioned stimulus; CS2 the second conditioned stimulus; CS3 the third conditioned stimulus; US, unconditioned stimulus; EXT, extinction session by repeated presentations of CS; RC retention control session in which no CS was presented b, Animals treated with scrambled control virus, fear conditioned and exposed to a novel context (RC SC shRNA) had significantly higher freezing scores than scrambled control animals that were fear conditioned followed by extinction (EXT SC shRNA), but this was blocked in animals that were treated with Adar1 shRNA and extinction trained (EXT Adar1 shRNA; n=5–8 animals per group from two combined independent cohorts, repeated two-way ANOVA, F1,21 = 67.17, ***p<.0001; Dunnett’s post-hoc tests: RC SC vs. EXT SC, * p = 0.0462, RC SC vs EXT Adar1 p = 0.3369, RC SC vs RC Adar1 p = 0.4407. c, This effect held at the second (repeated two-way ANOVA, F1,21 = 85.21, *p<.0001; Dunnett’s post-hoc tests: RC SC vs. EXT SC, ** p = 0.0065. RC SC vs EXT Adar1 p = 0.1568. RC SC vs RC Adar1 p = 0.2560), d, and third test (two-way ANOVA, F1,21 =27.56, *p<.0001; Dunnett’s post-hoc tests: RC SC vs. EXT SC, * p = 0.0404, RC SC vs EXT Adar1 p = 0.9994, RC SC vs RC Adar1 p = 0.6229). e, Schematic of the behavioral protocol used to test the effect of lentiviral-mediated knockdown of Adar1 on memory stability. f, There was no significant difference between SC and Adar1 shRNA animals subjected to repeated fear tests (RFT) on the first day of testing. g, However, at day 5 there was a significant difference between the SC and Adar1 shRNA (n = 5–7 animals per group from two combined independent cohorts, ANOVA, F1,9 = 5.571 *p<0.05; Bonferonni post-hoc test: SC vs Adar1 CS3 *p = 0.0326). There was also no significant difference between h, SC and Adar1 shRNA animals subjected to a single fear test (SFT) on day 5.