Figure 3

HDAC3 inhibition restores synaptic tagging and capture through the activation of Nuclear factor κB.

(A) Inhibition of HDAC3 failed to restore associativity in the aged neural networks when the activation of NFκB is prevented. WTET in S1 (open circles) after recording a stable baseline of 30 minutes resulted in potentiation significant up to 85 minutes after which it gradually decayed to baseline. STET in the presence of RGFP966 (10 μM) and Bay 11-7082 (30 μM) resulted in a significant potentiation in S2 (filled circles) that maintained for 4 hours (n = 6). Thus, STC was not expressed. (B) STET in the presence of Bay 11-7082 (30 μM) and RGFP966 (10 μM) induced a significant potentiation that lasted for 4 hours (n = 6). (C) STET in the presence of rapamycin (0.1 μM) resulted in potentiation that was significant up to 50 minutes. Afterwards, the potentiation rapidly decayed to baseline (n = 6). (D) Western blot analysis of hippocampal slices revealed increased levels of phospho-p65 in the ‘RGFP966 + STET’ group (Group iii) in comparison to ‘control’ (Group i), ‘STET’ group (Group ii) and ‘RGFP966 + Bay11-7082 + STET’ group (Group iv). (E) Histogram showing differences in the relative amount of phospho-p65 in control (Group i), ‘STET’ (Group ii), ‘RGFP966 + STET’ (Group iii) and ‘RGFP966 + Bay11-7082 + STET’ (Group iv) (one-way ANOVA, F = 17.33; P < 0.01). The values of the individual groups were calculated in relation to the control group while β-actin serves as a loading control. Each bar represents mean ± SEM of analysis of 5 blots per group. Asterisk indicates significant difference (Dunnett’s post hoc test, **P < 0.01). Symbols and traces are similar to Figs 1 and 2 except Fig. 3C which is similar to Fig. 1G and 2D.