Targeted resolution of G4-DNA by DHX36-dCas9 in the prelimbic cortex impairs fear memory. A, Pictorial of timeline for behavioral training and lentivirus infusion into the prelimbic region of the prefrontal cortex. B, After infusion of dCas9-DHX36 lentivirus into the prelimbic PFC, there was no significant impairment in acquisition for the Gphn or Chl1 guide. C, However, there was a significant impairment in recall for the Gphn guide in Context A (F_(2,11)= 17.31, **p < 0.01; Dunnett's post hoc test; CS1 control guide vs Gphn guide, *p = 0.0209; CS3 control guide vs Gphn guide, *p = 0.0298; CS3 control guide vs Gphn guide, ***p = 0.0002). D, In addition, following infusion of dCas9-DHX36 with either control guides, Gphn guides, or Chl1 guides, there was a significant reduction in G4-DNA at the Gphn locus following Gphn guide infusion (F_(2,24)= 3.574, *p < 0.05; Dunnett's post hoc test; control guide vs Gphn guide, *p = 0.0322). E, There was also a significant reduction in G4-DNA at the Chl1 locus with the Chl1 guides (F_(2,24)= 3.375, *p < 0.05; Dunnett's post hoc test; control guide vs Chl1 guide, *p = 0.0322).