Fig. 1: Postnatal Hdac2 deletion restricted to PV⁺ cells or Hdac2 inhibition before extinction training decrease the spontaneous recovery of fear memories after extinction in adult mice.

a Schematic representation of the experimental protocol. Ext. extinction. b Wild-type and PV-Cre; Hdac2^lox/lox littermates show efficient fear extinction. Repeated two-way ANOVA; F_genotype (1,22) = 4.430, P = 0.0470, F_extinction(11,242) = 8.864, P < 0.0001, F_genotype*_extinction (11,242) = 0.6427, P = 0.7911. Wild-type, but not PV-Cre; Hdac2^lox/lox littermates, show spontaneous recovery and context-dependent renewal of fear memory. Unpaired two-tailed t-tests, P = 0.0205 for fear retrieval; P = 0.0008 for fear renewal. Number of mice: Hdac2^lox/+ or Hdac2^lox/lox n = 14; PV-Cre; Hdac2^lox/lox n = 10. c In the absence of extinction training, PV-Cre; Hdac2^lox/lox mice show stable fear memory 10 days after conditioning, as control littermates (Mann–Whitney test, P = 0.2509). Number of mice: Hdac2^lox/+ or Hdac2^lox/lox n = 9; PV-Cre; Hdac2^lox/lox n = 7. d In the open field test, there is no significant difference in time spent in the center of the open field (unpaired two-tailed t-test, P = 0.4635) nor the total distance traveled (unpaired two-tailed t-test, P = 0.6083) between the two genotypes. Number of mice: Hdac2^lox/+ or Hdac2^lox/lox n = 12; PV-Cre; Hdac2^lox/lox n = 10. e In the elevated plus maze test, there is no genotype-dependent difference in time spent (unpaired two-tailed t-test, P = 0.3279) nor the number of entries in the open arms (unpaired two-tailed t-test, P = 0.1449). Number of mice: Hdac2^lox/+ or Hdac2^lox/lox n = 14; PV-Cre; Hdac2^lox/lox n = 12. f Schematic representation of the experimental protocol. Hdac2 inhibitor BRD6688 or the vehicle was injected intraperitoneally (i.p.) 6 h before the early extinction procedure. g One week after extinction training, freezing levels are significantly different in the spontaneous recovery test between vehicle- and BRD6688-injected Hdac2^lox/lox (h) but not between vehicle- and BRD6688-injected PV-Cre; Hdac2^lox/lox mice. g Extinction retrieval unpaired two-tailed t-test, P = 0.0030; fear renewal, unpaired two-tailed t-test, P = 0.1246. Number of Hdac2^lox/lox mice injected with vehicle, n = 10 or BRD6688, n = 9. h Extinction retrieval unpaired two-tailed t-test P = 0.0850, fear renewal unpaired two-tailed t-test P = 0.6733. Number of PV-Cre; Hdac2^lox/lox mice injected with vehicle, n = 10 or BRD6688, n = 8. Graph bars represent mean ± s.e.m. Circles represent individual mouse values. CS Conditioned stimulus, US Unconditioned stimulus. *P < 0.05, ***P < 0.001.