Hippocampal ERK2 dimerization regulates inhibitory avoidance memory reconsolidation and synaptic plasticity

Extensive research has examined extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in memory and synaptic plasticity, yet the mechanisms linking ERK activity to memory stabilization remain unclear. ERK dimerization is required for the activation of cytoplasmic targets involved in plasticity. Here, we investigated the role of ERK2 dimerization in long-term memory reconsolidation and synaptic plasticity. Reactivation of weak inhibitory avoidance (wIA) memory significantly reduced hippocampal ERK2 dimerization. Post-reactivation, intrahippocampal infusion of the ERK dimerization inhibitor DEL-22379 (DEL) produced bidirectional effects, impairing reconsolidation of strong inhibitory avoidance (sIA) memory, while enhancing reconsolidation of wIA memory. DEL administration efficiently blocked hippocampal ERK2 dimerization and impaired maintenance of high-frequency stimulation-induced long-term potentiation (LTP) in the hippocampal slices. These findings demonstrate that ERK2 dimerization occurs in the intact mouse brain and plays a critical role in IA memory and synaptic plasticity, highlighting its relevance in memory reconsolidation processes.