Temporal requirement of C/EBPβ in the amygdala following reactivation but not acquisition of inhibitory avoidance

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 ␤ (C/EBP␤) is essential only for the reconsolidation process. Moreover, the critical roles of both protein synthesis and C/EBP␤ 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/EBP␤ 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/EBP␤-dependent molecular pathway appears to be differentially recruited.

Intrahippocampal infusions of anisomycin produce amnesia: Contribution of increased release of norepinephrine, dopamine, and acetylcholine

“…These findings are consistent with those of many prior studies involving injections of protein synthesis inhibitors into the hippocampus (e.g., Bourtchouladze et al 1998;Quevedo et al 1999Quevedo et al , 2004Taubenfeld et al 2001;Barriantos et al 2002;Agnihotri et al 2004;Artinian et al 2007), as well as into other brain areas such as the amygdala (Nader et al 2000;Schafe and LeDoux 2000;Debiec et al 2002;Duvarci et al 2005;Parsons et al 2006;Milekic et al 2007), and prefrontal cortex (Santini et al 2004;Akirav and Maroun 2006;Touzani et al 2007). These reports are part of a large set of papers showing that direct brain injections of protein synthesis inhibitors produce amnesia for many tasks (cf.…”

The Activity-Regulated Cytoskeletal-Associated Protein (Arc/Arg3.1) Is Required for Memory Consolidation of Pavlovian Fear Conditioning in the Lateral Amygdala

“…Although the use of ODNs has proven successful in the hippocampus (Guzowski and McGaugh, 1997;Guzowski et al, 2000;Taubenfeld et al, 2001), fewer studies have used ODNs to manipulate gene expression in the amygdala (but see Malkani et al, 2004;Milekic et al, 2007). In our experiments, we show that intra-LA infusion of a biotinylated Arc/Arg3.1 ODN exhibits significant spread within the LA.…”

Limited efficacy of propranolol on the reconsolidation of fear memories

“…Toward this end, we used the same behavioral protocol that previously showed that IA reconsolidation is disrupted by post-retrieval administration of the protein synthesis inhibitors anisomycin and cycloheximide (Milekic and Alberini 2002;Milekic et al 2007) as well as of the antagonist of glucocorticoid receptors RU38486 (Taubenfeld et al 2008). Groups of rats were trained with 0.9 mA footshock intensity and tested 48 h later (Test 1).…”

“…The IA was performed as previously described (Milekic et al 2007). Briefly, the IA box (Model ENV-010MC, Med Associates) consisted of a lit (safe) compartment and a dark (shock) compartment separated by a door.…”