Role of ERK1/2 dimerization in memory and plasticity.

SANTIAGO OJEA RAMOS; MARÍA DEL CARMEN KRAWCZYK; CANDELA MEDINA; JULIETA MILLAN; ACUTAIN, MARIA FLORENCIA; BAEZ, MARÍA VERÓNICA; ARTURO GABRIEL ROMANO; BOCCIA, MARIANO; FELD, MARIANA

Congreso; SAN2022 Annual meeting; 2022

Sociedad Argentina de Neurociencia

While ERK1/2 phosphorylation has been extensively studied regarding memory andplasticity, little is known about the role of dimerization in those processes. Here we reportpreliminary results using native gel electrophoresis to assess the level of ERK2 dimerizationgenerated by glycine-induced chemical long-term potentiation (cLTP) in mature primarycultures of rat cortex neurons, and in mice hippocampus after inhibitory avoidance (IA)memory reactivation. We also evaluated the effect of DEL-22379, a recently developedspecific ERK dimerization inhibitor (non affecting phosphorylation), on IA memoryreconsolidation and cLTP. We found that cLTP induced ERK2 dimerization in mature culturedneurons, which was inhibited by DEL-22379 addition to the culture media. Additionally,memory reactivation induced a significant decrease of ERK2 dimerization in IA trained mice.Furthermore, intrahippocampal infusion of DEL-22379 after memory reactivation had asurprising bidirectional effect: while it blocked reconsolidation of a strong IA memory, theopposite effect was observed on reconsolidation of a weak IA memory, resulting in itsenhancement. This is the first report showing ERK dimerization in neuronal tissues and DEL-22379 effect on plasticity and memory processes. Although more research is needed, theseinitial findings suggest a relevant role of ERK dimerization in plasticity and memory