Systemic rapamycin disrupts the reconsolidation of context but not cued fear memory. Mean startle amplitudes of rats given an i.p. injection of either rapamycin (40 mg/kg) or vehicle immediately after memory reactivation, and tested in the same context in which they were trained or tested in a different context. (A) Context Fear, mean startle amplitude for pre-training noise-alone (black), and post-training noise-alone (white) trials 6 d after memory reactivation and the difference (± SEM) between the two (black and white stripes). Rapamycin-treated rats showed significantly less FPS to the conditioning context than vehicle-treated rats (*P < 0.05). None of the rats that were tested in a different context expressed context fear memory. (B) Cued Fear, mean startle amplitude for post-training noise-alone (dark gray), post-training odor-noise (light gray), and the difference (±SEM) between the two (gray and black stripes) 6 d after memory reactivation. There was no significant difference between rapamycin and vehicle treated rats in their expression of cued fear memory whether tested in the same or a different context from training.

Systemic rapamycin disrupts the consolidation of context but not cued fear memory. Mean startle amplitudes of rats given an i.p. injection of either rapamycin (40 mg/kg) or vehicle immediately after training, and tested in the same context in which they were trained or tested in a different context. (A) Context Fear, mean startle amplitude for pre-training noise-alone (black), and post-training noise-alone (white) trials, and the difference (± SEM) between the two (black and white stripes). Rapamycin-treated rats showed significantly less FPS to the conditioning context than vehicle-treated rats (*P < 0.05). None of the rats that were tested in a different context expressed context fear memory. (B) Cued Fear, mean startle amplitude for post-training noise-alone (dark gray), post-training odor-noise (light gray), and the difference (± SEM) between the two (gray and black stripes). There was no significant difference between rapamycin and vehicle-treated rats in their expression of cued fear memory whether tested in the same or a different context from training.

Single trial olfactory fear conditioning activates phosphorylation of p70s6K in the amygdala, which was prevented by post-training systemic rapamycin administration. Bars represent mean optical density values (± SEM) expressed as a percentage of home cage (HC), control (black), and GAPDH protein loading control. Representative blots of phosphorylated p70s6K are shown below their corresponding group. (A) Rats were presented with an odor cue and footshock that were either Paired (white) or Unpaired (gray), and were sacrificed 30 min or 60 min later. Another group, Context, was placed in the conditioning chamber for 7 min, without odor or shock exposure, and sacrificed 1 h later (striped). Olfactory fear conditioning is associated with an increase in phosphorylated p70s6K relative to HC, in the paired group at the 30 min post-training time point, as well as moderate enhancement at the 1-h time point, and in the unpaired groups at both 30-min and 1-h time points. These observed changes approached but did not reach statistical significance, P = 0.08. (B) Immediately after single-trial odor-shock training, rats were given i.p. rapamycin (RAP, striped) (40 mg/kg) or vehicle (VEH, dotted) and sacrificed 30 min later. There was significant increase in phosphorylated p70s6K relative to HC in the VEH group (*P < 0.05 compared to HC), and significantly less expression levels in the RAP group (#P < 0.05 compared to VEH and HC).