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

FREUDENTHAL R,; BOCCIA MM,; BLAKE MG; DE LA FUENTE V; ACOSTA GB; BARATTI CM; ROMANO A

JOURNAL OF NEUROSCIENCE

SFN

Lugar: Washington; Año: 2007 vol. 27 p. 13436 - 13445

0270-6474

Initially,memoryis 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-kB (NF-kB) in memory consolidation. Here, we demonstrate that the inhibition of NF-kB after memory reactivationimpairs retention of a hippocampal-dependent inhibitory avoidance task in mice.Weused two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IkB kinase), the kinase that activates NF-kB. Second, we infused intracerebroventricular or intrahippocampal kB decoy, a direct inhibitor of NF-kB consisting of a double-stranded DNA oligonucleotide that contains the kB consensus sequence. When injected immediately after memory retrieval, sulfasalazine or kBdecoy (Decoy) impaired long-term retention. In contrast, a one base mutated kBdecoy (mDecoy) had no effect. Furthermore, we also found NF-kB 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-kB is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.kB (NF-kB) in memory consolidation. Here, we demonstrate that the inhibition of NF-kB after memory reactivationimpairs retention of a hippocampal-dependent inhibitory avoidance task in mice.Weused two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IkB kinase), the kinase that activates NF-kB. Second, we infused intracerebroventricular or intrahippocampal kB decoy, a direct inhibitor of NF-kB consisting of a double-stranded DNA oligonucleotide that contains the kB consensus sequence. When injected immediately after memory retrieval, sulfasalazine or kBdecoy (Decoy) impaired long-term retention. In contrast, a one base mutated kBdecoy (mDecoy) had no effect. Furthermore, we also found NF-kB 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-kB is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.