Memory reconsolidation of an inhibitory avoidance task in mice involves cytosolic ERK2 bidirectional modulation

- Cytosolic ERK2, but not ERK1, activity increases 15 min after IA memory retrieval and decreases 45 min after it.
- PD098059 impairs retention performance in a dose-dependent manner when given in the dHIP immediately after retrieval.
- Hippocampal ERK inhibition did not alter memory reconsolidation when administered without retrieval or 3 h after it.
- ERK inhibition by PD098059 administration in the dHIP 40 min after retrieval of a weak memory enhanced mice performance.

Reconsolidation has been defined as the process of memory stabilization after retrieval involving, among others, gene expression regulation and post-translational modifications. Many of these mechanisms are shared with memory consolidation. Here, we studied hippocampal ERK participation on memory reconsolidation of an inhibitory avoidance task in CF-1 mice. We found a retrieval-induced cytosolic ERK2 activation in the hippocampus (HIP) 15 min after memory reactivation, and an inhibition at 45 min. PD098059, a MEK1/2 (MAPK/ERK kinase) inhibitor, administered in the HIP immediately after retrieval impaired memory in a dose-dependent fashion. However, infusions of the highest dose of PD098059 performed 40 min after retrieval enhanced memory in mice trained with a weaker footshock. These results suggest for the first time that ERK2 is involved in memory reconsolidation in a biphasic fashion. Furthermore, the inhibition of ERK could either impair or enhance mice performance depending on ERK state of activation.