Hippocampal ERK2 dimerization regulates inhibitory avoidance memory reconsolidation and synaptic plasticity.

Area of Science:

• Neuroscience
• Molecular Biology
• Cognitive Science

Background:

• Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation is extensively studied in memory and synaptic plasticity.
• The precise mechanisms linking ERK activity to memory stabilization are not fully understood.
• ERK dimerization is a prerequisite for activating cytoplasmic targets involved in neural plasticity.

Purpose of the Study:

• To investigate the role of ERK2 dimerization in long-term memory reconsolidation.
• To examine the impact of ERK2 dimerization on synaptic plasticity in the hippocampus.

Main Methods:

• Investigated ERK2 dimerization in mice during memory reactivation.
• Utilized the ERK dimerization inhibitor DEL-22379 (DEL) via intrahippocampal infusion.
• Assessed memory reconsolidation of weak inhibitory avoidance (wIA) and strong inhibitory avoidance (sIA) memories.
• Measured high-frequency stimulation-induced long-term potentiation (LTP) in hippocampal slices.

Main Results:

• Reactivation of wIA memory led to a significant decrease in hippocampal ERK2 dimerization.
• Infusion of DEL-22379 impaired sIA memory reconsolidation but enhanced wIA memory reconsolidation.
• DEL administration effectively blocked hippocampal ERK2 dimerization.
• Impaired maintenance of LTP in hippocampal slices following DEL administration.

Conclusions:

• ERK2 dimerization occurs in the intact mouse brain.
• ERK2 dimerization plays a critical role in inhibitory avoidance memory.
• ERK2 dimerization is essential for synaptic plasticity and memory reconsolidation processes.