Activation of hippocampal nuclear factor-kappa B by retrieval is required for memory reconsolidation.
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-kappaB (NF-kappaB) in memory consolidation. Here, we demonstrate that the inhibition of NF-kappaB 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 (IkappaB kinase), the kinase that activates NF-kappaB. Second, we infused intracerebroventricular or intrahippocampal kappaB decoy, a direct inhibitor of NF-kappaB consisting of a double-stranded DNA oligonucleotide that contains the kappaB consensus sequence. When injected immediately after memory retrieval, sulfasalazine or kappaB decoy (Decoy) impaired long-term retention. In contrast, a one base mutated kappaB decoy (mDecoy) had no effect. Furthermore, we also found NF-kappaB 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-kappaB is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.
Laboratorio de Neurofarmacología de Procesos de Memoria, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mariano
M
Boccia
Ramiro
R
Freudenthal
Mariano
M
Blake
Veronica
V
de la Fuente
Gabriela
G
Acosta
Carlos
C
Baratti
Arturo
A
Romano
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012460:Sulfasalazine / Q000008:administration & dosage
D016328:NF-kappa B; D012460:Sulfasalazine