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.