Figure 8.

Etoposide infusion into the PLPFC inhibits fear memory formation by blocking repair of DSBs. A, Time course of behavioral training and etoposide infusion. B, There were no significant differences between etoposide (0.1 μg/side) and control groups in percentage freezing during fear acquisition. C, There was a significant decrease in the percentage freezing for animals infused with etoposide compared with control at test (N = 9–12 per group). D, Etoposide infusion blocked the temporal accumulation of 5-mC within the promoter region of Arc, (E) c-Fos, (F) Npas4, and (G) Cyr61. H, Etoposide infusion also inhibited Gadd45γ occupancy at promoter of Arc at the 5 h time point, (I) c-Fos, (J) Npas4, and (K) Cyr61. Etoposide led to a significant decrease in mRNA at 5 h post-training (L) Arc, (M) c-Fos, (N) Npas4, and (O) Cyr61. Etoposide infusion had no effect on Arc, c-Fos, Npas4, and Cyr61 mRNA expression at the 0 h time point (L–O). N = 4 per group for D–O. FC, Fear conditioned; CTX, context exposure. Error bars represent SEM. * p < 0.05, ** p < 0.01, *** p < 0.001.