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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 3. Z-DNA is a critical modulator of activity-dependent transcription.

Figure 3.

Animals that were exposed to the fear conditioning context but not conditioned (Ctx A) compared to those that were fear conditioned and euthanized immediately after training (FC O h), 1 h after (FC 1h), or 5 h after (FC 5h) exhibited significantly increased Z-DNA at the a, Nrxn3 locus (n = 5–6 animals per group from a single cohort, ANOVA, F3,18 = 5.983, *p<0.01 Dunnett’s posthoc tests: Ctx A vs FC 0h p = 0.0083, Ctx A vs FC 1h p = 0.4994, Ctx A vs FC 5h 0.9694), b, Car5a locus (ANOVA, F3,18 = 5.419, *p<0.01 Dunnett’s post-hoc tests: Ctx A vs FC 0h p = 0.0344, Ctx A vs FC 1h p = 0.9087, Ctx A vs FC 5h p = 0.6681) c, Inst2 (ANOVA, F3,18 = 5.459, *p<0.01; Dunnett’s post-hoc tests: Ctx A vs FC 0h p = 0.0142, Ctx A vs FC 1h p = 0.999, Ctx A vs FC 5h p = 0.9496), and f, Snap47 locus (ANOVA, F3,18 = 5.214, *p<0.01, Dunnett’s post-hoc tests: Ctx A vs FC 0h p = 0.0209, Ctx A vs FC 1h p = 0.9807, Ctx A vs FC 5h p = 0.9316). d, Model depicting the transition from B-DNA to Z-DNA during fear conditioning and from Z-DNA to B-DNA during fear extinction. There was also a significant alteration in Z-DNA when comparing fear-trained animals exposed to a novel context following fear conditioning (retention control: RC) to fear-conditioning followed by 10CS (EXT 10), 30CS (EXT 30), or 60CS extinction (EXT 60). Specifically, Z-DNA significantly decreased at the e, Nrxn3 locus (n = 6–8 animals per group from a single cohort, ANOVA F3,23 = 39.48 ****p<0.0001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.0879 RC vs EXT 30 ****p <0.0001, RC vs EXT 60 <0.0001), i, Car5a locus (ANOVA F(3,22) = 32.94 ****p<0.0001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.9031 RC vs EXT 30 ****p <0.0001, RC vs EXT 60 ****p<0.0001), f, Inst2 locus (ANOVA, F3,25 = 13.88, ****p<0.0001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.9920, RC vs EXT 30 p = 0.0009, RC vs EXT 60 p = 0.0002), and g, Snap47 locus (ANOVA, F3,23 = 34.88, ****p<0.0001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.3363, RC vs EXT 30 ****p < 0.0001, RC vs EXT 60 ****p<0.0001).