Figure 4.
MEK signaling through ERK contributes to long-term fear memory and contextual fear conditioning-induced changes in histone H3. (A) Quantification of freezing behavior 24 h following the training period. Animals that were fear conditioned and injected with DMSO (2.99 mL/kg, n = 4) displayed significantly greater freezing than either naive animals (naive, n = 4) or animals that were fear-conditioned and injected with SL327 (100 mg/kg, n = 7). Naive animals had not been previously exposed to either the training chamber or shocks. (B) Quantification of immunoblot densities for phospho-ERK and total ERK. Injection of animals with SL327 (100 mg/kg) following fear conditioning (FC + SL327, n = 9) significantly reduced ERK2 phosphorylation in area CA1 compared with injection with DMSO (2.99 mL/kg) following fear conditioning (FC + DMSO, n = 3). Total ERK was unchanged. Representative immunoblots for P-ERK and total ERK are shown for each condition. Control (C) samples appear on the left and experimental (E) samples appear on the right. (C) Quantification of immunoblot densities for phospho-histone H3, acetyl-histone H3, and phospho-acetyl-histone H3. Injection of animals with SL327 (100 mg/kg) following fear conditioning (FC + SL327, n = 3) significantly reduced histone H3 phosphorylation, acetylation, and phospho-acetylation in area CA1 compared with injection with DMSO (2.99 mL/kg) following fear conditioning (FC + DMSO, n = 3). Total histone H3 was unchanged. Representative immunoblots for P-H3 and total H3 are shown for each condition. Control (C) samples appear on the left, and experimental (E) samples appear on the right. Error bars indicate standard error of the mean. Asterisks denote significant differences (P < 0.05) as determined by Tukey’s multiple comparison test.
