Figure 8.

Inhibition of HDAC1 activity during fear extinction increases H3K9ac and c-Fos expression. A, Mice that were injected intrahippocampally with MS-275 after each extinction trial exhibited impaired fear extinction when compared with vehicle-treated mice (n = 5/group; p < 0.01). Hippocampal tissue was prepared for molecular analysis 1 h after exposure to E5. B, ChIP analysis of the c-Fos promoters revealed elevated H3K9 acetylation and reduced H3K9 trimethylation in MS-275-injected mice when compared with the control group (*p < 0.01 vs vehicle). C, qPCR shows increased hippocampal −cFos and levels in MS-275-treated mice (*p < 0.05 vs vehicle). D–F, Hippocampal tissue that was obtained 1 h after E5 from the same mice used in the behavior experiment shown in Figure 4D was used for molecular analysis. HDAC1 siRNA-treated mice (n = 5) display reduced HDAC1 levels (D), increased H3K9 acetylation and decreased H4K9 methylation (E) at the cFos promoter while cFos expression was increased (F) when compared with scrambled RNA-treated mice (n = 4, *p < 0.05). Error bars indicate SEM.