Figure 4.

Hippocampal HDAC1 affects the extinction of fear memories. A, Top, Experimental design. Bottom, While AAV-HDAC1-GFP and AAV-GFP-injected mice (n = 10/group) show similar freezing behavior on E1, fear extinction learning was significantly enhanced in the AAV-HDAC1-GFP group (*p < 0.05, **p < 0.01 for day comparison; repeated measurements p = 0.001, F = 12,78). B, Top, Experimental design. Bottom, When compared with the vehicle group (n = 21), intrahippocampal injection of MS-275 (n = 21) immediately after each extinction trial impaired fear extinction (*p < 0.05 for day comparison; repeated measurements p = 0.0038, F = 9,435). C, Intrahippocampal injection of MS-275 does not affect the consolidation of contextual fear memories. Microcannulae were implanted into the hippocampus of mice (n = 7/group). After recovery all animals were subjected to contextual fear conditioning. Immediately after the training mice were injected with the same concentration of MS-275 that was used for fear extinction experiments fear memory was analyzed 24 h later. Notably, freezing behavior during the memory test was similar between MS-275 and vehicle-injected mice. D, Left, Experimental design. Right, When compared with the control group that received a scrambled control RNA (n = 6), intrahippocampal injection of HDAC1 siRNA (n = 6) impaired fear extinction (*p < 0.05, **p < 0.001 for day comparison; repeated measurements p = 0.0001, F = 21,89). E, HDAC1 siRNA-treated mice display significantly reduced hippocampal levels of Hdac1 mRNA and HDAC1 protein, measured via qPCR and quantitative immunoblot respectively (n = 5/group)**p < 0.001 vs scrambled RNA). Error bars indicate SEM.