PMC

The reconsolidation deficit induced by c646 is not sensitive to spontaneous recovery, reinstatement, or to a shift in testing context. (A) Schematic of the behavioral protocol (see text for details). (B) Memory retrieval data for rats given intra-LA infusion of Vehicle (n = 6) or c646 (n = 6). (*) P < 0.05 relative to the pre-CS period. (C) Mean (±SEM) percent freezing during the PR-STM and PR-LTM tests in Vehicle- and c646-infused rats. (*) P < 0.05 relative to Vehicle-infused controls. (D) Mean (±SEM) percent freezing during the spontaneous recovery, reinstatement, and context shift tests. (E) Cannula placements for rats infused with either Vehicle (black circles) or c646 (gray circles). (*) P < 0.05 relative to Vehicle-infused controls.

Intra-LA infusion of an inhibitor of p300/CBP activity impairs the reconsolidation of a “well-consolidated” fear memory. (A) Rats were fear-conditioned with three tone–shock pairings. Two weeks following training, rats were given a memory reactivation session consisting of a single-tone CS presentation followed 1 h later by intra-LA infusion of Vehicle (n = 5) or c646 (500 ng/side; n = 6). (B) Memory retrieval data for the Vehicle- and c646-infused groups. (*) P < 0.05 relative to the pre-CS period. (C) Mean (±SEM) percent freezing during the PR-STM and PR-LTM tests in Vehicle- and c646-infused rats. (D) Cannula placements for rats infused with either Vehicle (black circles) or c646 (gray circles). (*) P < 0.05 relative to Vehicle-infused controls.

Intra-LA infusion of an inhibitor of p300/CBP activity impairs fear memory consolidation and the consolidation of training-related neural plasticity in the LA. (A) Rats were given two baseline AEFP recording sessions on separate days followed by fear conditioning with three tone-pip–shock pairings followed 1 h later by intra-LA infusion of either Vehicle (n = 8) or c646 (500 ng/side; n = 7). Rats in each group were then tested for STM and LTM 3 and 21 h later while AEFPs were recorded from the LA. (B) Mean (±SEM) percent freezing during the STM and LTM tests in Vehicle- and c646-infused groups. (C) Mean (±SEM) percent of change in AEFP amplitude during the STM and LTM tests in Vehicle- and c646-infused rats, relative to baseline. (*) P < 0.05 relative to Vehicle-infused controls. (D) Representative AEFPs recorded from the LA for each group during baseline (light gray trace), STM and LTM sessions (darker traces). Scale bar, 10 µV, 5 msec. (E) Electrode placements for rats infused with either Vehicle (black circles) or c646 (gray circles).

Intra-LA infusion of an inhibitor of p300/CBP activity in the absence of fear memory retrieval has no effect on fear memory reconsolidation or memory-related neural plasticity in the LA. (A) Rats were given two baseline AEFP recording sessions on separate days followed by fear conditioning with three tone-pip–shock pairings. Twenty-four hours following training, rats were given a “no-reactivation” session followed by infusion of Vehicle (n = 7) or c646 (500 ng/side; n = 6). Rats in each group were then tested for “PR”-STM and “PR”-LTM 3 and 21 h later while AEFPs were recorded from the LA. (B) Memory retrieval data for the Vehicle- and c646-infused groups. (C) Mean (±SEM) percent freezing during the “PR”-STM and “PR”-LTM tests in Vehicle- and c646-infused groups. (D) Mean (±SEM) percent of change in AEFP amplitude during the “PR”-STM and “PR”-LTM tests in Vehicle- and c646-infused rats, relative to baseline. (E) Representative AEFPs recorded from the LA for each group during baseline (light gray trace), “PR”-STM and “PR”-LTM sessions (darker traces). Scale bar, 10 µV, 5 msec. (F) Electrode placements for rats infused with either Vehicle (black circles) or c646 (gray circles).

Intra-LA infusion of an inhibitor of p300/CBP activity impairs training-related acetylation of histone H3 and fear memory consolidation. (A) Schematic of the behavioral protocol. Rats were fear-conditioned with three tone–shock pairings followed 1 h later by intra-LA infusion of either Vehicle (n = 8) or c646 (500 ng/side; n = 8) and were sacrificed 30 min later. A third group did not receive conditioning and was infused with Vehicle before sacrifice (n = 7). Separate groups of rats were fear-conditioned with three tone–shock pairings followed 1 h later by intra-LA infusion of either Vehicle (n = 9) or c646 (500 ng/side; n = 7) and tested for STM and LTM 3 and 21 h later, respectively. (B) Western blot analysis of acetylated and total (nonacetylated) histone H3 from LA homogenates from naive (N)–Vehicle, fear-conditioned (FC)–Vehicle, and FC–c646 groups. (*) P < 0.05 relative to FC–Vehicle and N–Vehicle groups. (Inset) Representative Western blots. (C) Mean (±SEM) percent freezing during the STM and LTM tests in Vehicle- and c646-infused groups. A third group is depicted that received infusion of either Vehicle (n = 8) or c646 (n = 6) 6 h following fear conditioning (“delayed infusion”) followed by an LTM test 21 h later. (D) Cannula placements for rats infused with either Vehicle (black circles) or c646 (gray circles). (*) P < 0.05 relative to Vehicle-infused controls.

Intra-LA infusion of an inhibitor of p300/CBP activity impairs fear memory reconsolidation and memory-related neural plasticity in the LA. (A) Rats were given two baseline AEFP recording sessions on separate days followed by fear conditioning with three tone-pip–shock pairings. Twenty-four hours following training, rats were given a memory reactivation session consisting of a single tone-pip CS presentation followed 1 h later by intra-LA infusions of Vehicle (n = 5) or c646 (500 ng/side; n = 6). Rats in each group were then tested for PR-STM and PR-LTM 3 and 21 h later while AEFPs were recorded from the LA. (B) Memory retrieval data for the Vehicle- and c646-infused groups. (*) P < 0.05 relative to the pre-CS period. (C) Mean (±SEM) percent freezing during the PR-STM and PR-LTM tests in Vehicle- and c646-infused groups. (D) Mean (±SEM) percent of change in AEFP amplitude during the PR-STM and PR-LTM tests in Vehicle- and c646l-infused rats, relative to baseline. (*) P < 0.05 relative to Vehicle-infused controls. (E) Representative AEFPs recorded from the LA for each group during baseline (light gray trace), PR-STM and PR-LTM sessions (darker traces). Scale bar, 10 µV, 5 msec. (F) Electrode placements for rats infused with either Vehicle (black circles) or c646 (gray circles).

Intra-LA infusion of an inhibitor of p300/CBP activity impairs retrieval-related acetylation of histone H3 in the LA and fear memory reconsolidation. (A) Schematic of the behavioral protocol. Rats were fear-conditioned with three tone–shock pairings. Twenty-four hours following training, rats were given a memory reactivation session consisting of a single-tone CS presentation followed 1 h later by intra-LA infusions of Vehicle (n = 8) or c646 (500 ng/side; n = 7). All rats were sacrificed 30 min following infusion. A third group did not receive conditioning or retrieval testing and was infused with Vehicle before sacrifice (n = 7). Separate groups of rats were fear-conditioned followed 24 h later by a memory reactivation session consisting of a single-tone CS presentation followed 1 h later by intra-LA infusion of Vehicle (n = 9) or c646 (500 ng/side; n = 8). Two additional groups of rats were given a “no-reactivation” session followed by infusion of Vehicle (n = 7) or c646 (500 ng/side; n = 6). All rats were then tested for PR-STM and PR-LTM 3 and 21 h later, respectively. (B) Cannula placements for rats infused with either Vehicle (black circles) or c646 (gray circles). (C) Memory retrieval data for the Reactivated (R)–c646 and R–Vehicle groups used in the Western blotting experiments. (*) P < 0.05 relative to the pre-CS period. (D) Western blot analysis of acetylated and total histone H3 from LA homogenates taken from Naive (N)–Vehicle, R–Vehicle, and R–c646 groups. (*) P < 0.05 relative to R–Vehicle and N–Vehicle groups. (Inset) Representative Western blots. (E) Memory retrieval data for the Reactivated (R)–c646 and R–Vehicle groups in the behavioral experiments. (*) P < 0.05 relative to the pre-CS period. (F) Mean (±SEM) percent freezing during the PR-STM and PR-LTM tests in R–Vehicle and R–c646 groups. A third group is depicted that received infusion of either Vehicle (n = 9) or c646 (n = 6) 6 h following retrieval (“delayed infusion”) followed by a PR-LTM test 21 h later. (*) P < 0.05 relative to Vehicle-infused controls. (G) Memory retrieval data for the Non-reactivated (NR)–c646 and NR–Vehicle groups. (H) Mean (±SEM) percent freezing during the “PR”-STM and “PR”-LTM tests in NR–Vehicle and NR–c646 groups.