Role of ERK1/2 dimerization in memory and plasticity

OJEA RAMOS, SANTIAGO; MEDINA C; MILLAN J; KRAWCZYK M; ACUTAIN MF; BAEZ MV; ROMANO A; BOCCIA MM; FELD M

CABA

Congreso; XXXVII Reunion anual de la SAN; 2022

Sociedad Argentina de Investigaciones en Neurociencias

While ERK1/2 phosphorylation has been extensively studied regarding memory and plasticity, little is known about the role of dimerization in those processes. Here we report preliminary results using native gel electrophoresis to assess the level of ERK2 dimerization generated by glycine-induced chemical long-term potentiation (cLTP) in mature primary cultures of rat cortex neurons, and in mice hippocampus after inhibitory avoidance (IA) memory reactivation. We also evaluated the effect of DEL-22379, a recently developed specific ERK dimerization inhibitor (non affecting phosphorylation), on IA memory reconsolidation and cLTP.We found that cLTP induced ERK2 dimerization in mature cultured neurons, 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 a surprising bidirectional effect: while it blocked reconsolidation of a strong IA memory, the opposite effect was observed on reconsolidation of a weak IA memory, resulting in its enhancement.This is the first report showingon ERK dimerization in neuronal tissues and DEL-22379 effect on plasticity and memory processes. Although more research is needed, these initial findings suggest a relevant role of ERK dimerization in plasticity and memory.