Activation of Hippocampal Nuclear Factor-κB by Retrieval Is Required for Memory Reconsolidation

Abstract

Initially, memory is labile and requires consolidation to become stable. However, several studies support that consolidated memories can undergo a new period of lability after retrieval. The mechanistic differences of this process, termed reconsolidation, with the consolidation process are under debate, including the participation of hippocampus. Up to this point, few reports describe molecular changes and, in particular, transcription factor (TF) involvement in memory restabilization. Increasing evidence supports the participation of the TF nuclear factor-B (NF-B) in memory consolidation. Here, we demonstrate that the inhibition of NF-B after memory reactivation impairs retention of a hippocampal-dependent inhibitory avoidance task in mice. We used two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IB kinase), the kinase that activates NF-B. Second, we infused intracerebroventricular or intrahippocampal B decoy, a direct inhibitor of NF-B consisting of a double-stranded DNA oligonucleotide that contains the B consensus sequence. When injected immediately after memory retrieval, sulfasalazine or B decoy (Decoy) impaired long-term retention. In contrast, a one base mutated B decoy (mDecoy) had no effect. Furthermore, we also found NF-B activation in the hippocampus, with a peak 15 min after memory retrieval. This activation was earlier than that found during consolidation. Together, these results indicate that NF-B is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.

Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation

“…This recovery depended on memory reactivation, and only occurred if the treatment was administered within a temporal window. Besides, to provide compelling evidence that Ch acts specifically on the mechanisms mediating memory reconsolidation, as opposed to producing nonspecific effects, it is necessary to show that the change does not occur shortly after retrieval, but is observed later (Boccia et al, 2007;Nader et al, 2000). Along this line, we observed that Ch was effective only when T2 was delayed enough from T1.…”

“…However, to add evidence that the pharmacological actions of Ch are exerted on memory reconsolidation the effects of Ch should not be seen in a retention test performed shortly after retrieval, as was already shown blocking protein synthesis (Nader, Schafe, & LeDoux, 2000) and using NF-B inhibitors (Boccia et al, 2007).…”

Pharmacological effects and behavioral interventions on memory consolidation and reconsolidation

“…Short-term memory was not affected by post-retrieval intra-hippocampal injections of κBdecoy, whereas its effect on LTM persisted for more than 3 weeks, C.M. Baratti et al www.bjournal.com.br without signs of spontaneous recovery (13).…”

“…NF-κB is also activated in the hippocampus by memory retrieval, and is probably involved in restabilization of the original memory, but its activation occurs earlier in memory reconsolidation than in memory consolidation: the peak of NF-κB activation takes place 15 min after memory reactivation (13).…”

“…We shall consider in this article the effects of intracerebroventricular (icv ) infusions of hemicholinium (HC-3), a central inhibitor of acetylcholine (Ach) synthesis (7), of intraperitoneal administration of N ω -nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of nitric oxide synthase (NOS; 8), on post-training (memory consolidation) and post-reactivation (memory reconsolidation), and Memory consolidation and reconsolidation www.bjournal.com.br of intrahippocampal injections of an inhibitor of the transcription factor (nuclear factor κB, NF-κB; 9) on retention performance of an inhibitory avoidance response in mice (10)(11)(12)(13). We also will briefly discuss both the posttraining and the post-retrieval effects of the exposure of mice to a new learning experience (14).…”