Memory changes are assessed by the overall freezing percentage. (A) There are no baseline freezing changes between the genotypes (no differences in baseline freezing levels between graphs B, C, or D, so subjects were combined; p>0.05). (B) DKO mice show memory deficits at 1 wk and 1 mo compared to WT mice. AC8 rescue mice reveal that replacing AC8 expression within the forebrain of DKO mice throughout training, retention and testing is sufficient to rescue CF memory deficits (n = 9–11/genotype, *p≤0.05 AC8 vs DKO). Turning AC8 off during (C) CF training (n = 8–10, *p≤0.05, AC8 and DKO vs WT) or (D) during the retention period (n = 9–11, *p≤0.01, AC8 and DKO vs WT) prevents restoration of the memory deficits. Furthermore, AC8 rescue mice still show memory deficits after turning AC8 back on for 2 wks after having it off since training (n = 9–11, *p≤0.05, AC8 and DKO vs WT). AC8 on = doxycycline off; Symbols: Tr, training; Wk, week; Mo, month.