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. 2007 Jul 18;14(7):504-11.
doi: 10.1101/lm.598307. Print 2007 Jul.

Temporal Requirement of C/EBPbeta in the Amygdala Following Reactivation but Not Acquisition of Inhibitory Avoidance

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Free PMC article

Temporal Requirement of C/EBPbeta in the Amygdala Following Reactivation but Not Acquisition of Inhibitory Avoidance

Maria H Milekic et al. Learn Mem. .
Free PMC article

Abstract

Following learning, a memory is fragile and undergoes a protein synthesis-dependent consolidation process in order to become stable. Established memories can again become transiently sensitive to disruption if reactivated and require another protein synthesis-dependent process, known as reconsolidation, in order to persist. Here, we show that, in the basolateral amygdala (BLA), protein synthesis is necessary for both consolidation and reconsolidation of inhibitory avoidance (IA) memory, while the expression of the transcription factor CCAAT enhancer binding protein beta (C/EBPbeta) is essential only for the reconsolidation process. Moreover, the critical roles of both protein synthesis and C/EBPbeta following IA reactivation are temporally restricted, as they are necessary only for recent but not old IA memories. These results, together with previous findings showing that in the hippocampus both protein synthesis and C/EBPbeta expression are required for consolidation but not reconsolidation of IA indicate that the stabilization process that takes place either after training or memory retrieval engages distinct neural circuits. Within these circuits, the C/EBPbeta-dependent molecular pathway appears to be differentially recruited.

Figures

Figure 1.
Figure 1.
IA memory consolidation and reconsolidation require protein synthesis in the BLA. (A) IA memory consolidation requires protein synthesis in the BLA. Injection of anisomycin (Ani; n = 8) into the BLA immediately after training significantly impairs memory retention at 48 h compared to vehicle (Veh; n = 8; *P < 0.05). (B) IA memory reconsolidation requires protein synthesis in the BLA. Anisomycin (Ani; n = 8;) injected into the BLA immediately following reactivation (Test 1) significantly impairs memory retention at 96 h after training (Test 2) compared to vehicle (Veh; n = 7; ***P < 0.001) and compared to its Test 1 retention latency (**P < 0.01). Rats that did not undergo reactivation (No Reactivation) and were injected into the BLA with anisomycin had normal memory retention at 96 h after training. Temporal diagrams beside each graph illustrate injection, training, and testing time points. All values are expressed as mean latency ± SEM.
Figure 2.
Figure 2.
C/EBPβ in the BLA is not required for IA consolidation. (A) Biotinylated β-ODN diffusion and stability after injection into the BLA. Representative brain sections at −2.8 mm from bregma of animals injected with biotinylated β-ODN and euthanized 2 h or 8 h after injection. (B) C/EBPβ is not required in the BLA for IA memory consolidation. Training, testing, and injection time points are illustrated in a temporal diagram. β-ODN or SC-ODN was injected bilaterally into the BLA at the following time points: 1 h before training (−1 h, n = 7/group), immediately after (0 h, SC-ODN n = 10, β-ODN n = 8), 0 + 2 h (0 + 2 h, n = 12/group), 5 h (5 h, n = 8/group), or 5 + 12 h (n = 8/group) after training. No significant difference in latency was observed among β-ODN- and SC-ODN-treated rats at any of the injection time points. All values are expressed as mean latency ± SEM.
Figure 3.
Figure 3.
C/EBPβ is required in the BLA for IA memory reconsolidation. (A) β-ODN injected in the BLA immediately after reactivation does not affect IA memory reconsolidation. Rats were injected bilaterally into the BLA with either β-ODN (n = 8) or SC-ODN (n = 8) immediately after retrieval (Test 1) at 48 h after training. When re-tested for memory retention 48 h later (Test 2, 96 h after training), all rats had similar latencies. (B) β-ODN-injected into the BLA 5 h after reactivation impairs IA memory. Rats injected with β-ODN (n = 11) 5 h after memory reactivation (Test1) had significantly lower retention latencies when retested 48 h later (Test 2, 96 h post-training) compared to rats injected with SC-ODN (n = 9, ***P < 0.001). Animals receiving β-ODN (n = 8) 48 h after training, but in the absence of reactivation (No Reactivation), had strong retention when tested at 96 h. These latencies were not significantly different from those of rats that received SC-ODN (n = 8). Temporal diagrams next to each graph depict injection, training, and testing time points. (C) Representative brain section of BLA tissue punches. (D) Densitometric analysis of Western blots (one representative sample per treatment is shown) of BLA punches extracts (n = 4/group) immunostained with anti-C/EBPβ. Data are expressed as mean % ± SEM of the SC-ODN (100%) control mean values. C/EBPβ values were normalized to those of actin.
Figure 4.
Figure 4.
Disruption of either protein synthesis or C/EBPβ in the BLA following reactivation does not affect the retention of a 2-wk-old IA memory. (A) Rats injected with anisomycin (Ani; n = 8) into the BLA immediately after reactivation, 2 wk after training (Test 1), maintained very strong latencies when retested 48 h later (Test 2) and were not significantly different from rats injected with vehicle solution (Veh, n = 8). (B) Rats injected with β-ODN (n = 9) into the BLA immediately after reactivation, 2 wk after training (Test 1), maintained very strong latencies when retested 48 h later (Test 2). These latencies were similar to the Test 2 latencies of rats injected with SC-ODN (n = 8). Temporal diagrams next to each graph depict injection, training, and testing time points. Values are expressed as mean latency ± SEM.

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