Figure 1

HDAC3 inhibition in aged neural networks augments LTP.

(A) Schematic representation of a hippocampal slice depicting the location of electrodes in CA1 region for field-EPSP recording: Stimulating electrode was positioned in stratum radiatum to stimulate Schaeffer collateral and recording electrode was positioned onto CA1 apical dendrites. (B) The STET resulted in potentiation that maintained for 4 hours (n = 8). (C) The induction of LTP in the presence of HDAC3 inhibitor, RGFP966 (10 μM) resulted in augmented potentiation that lasted for 4 hours (n = 9). (D) A histogram of mean fEPSP slope values recorded for ‘STET’ groups and ‘RGFP966 + STET’ groups at the time points −15 minute (baseline), +60 minute and +240 minute analyzed with two-way ANOVA. Analysis between groups with Tukey’s multiple comparisons test showed significant differences between the ‘STET’ and ‘RGFP966 + STET’ groups at 60 minute (P < 0.05) and 240 minute (P < 0.001). (E) STET coupled with co-application of RGFP966 (10 μM) and Emetine (20 μM) resulted in a potentiation that decayed back to baseline (n = 6). (F) STET could not induce potentiation in the presence of APV (50 μM) and RGFP966 (10 μM) (n = 3). (G) The bath application of RGFP966 (10 μM) did not significantly alter the baseline responses (n = 6). Three solid arrows in all the figures represent the STET for the induction of late-LTP. Representative fEPSP traces shown in B to E were recorded at -15 min (solid line); 75 minute (dotted line) and 240 minute (hatched line) after LTP induction. In F, the post induction traces are from +30 and +60 min whereas in G it represents +75 and +180 min. Scale bars for all the traces vertical: 3 mV; horizontal: 5 ms. Asterisks indicate significant differences between groups (Tukey’s post hoc test, *P < 0.05, **P < 0.001, ***P < 0.0001). Error bars indicate ± SEM.