133 | Beyond Phosphorylation: ERK2 dimerization influence on memory and plasticity.

Cognition, Behavior, and Memory

Author: Santiago Ojea Ramos | Email: ojea.santiago@gmail.com

Santiago Ojea Ramos , María del Carmen Krawczyk , Candela Medina , Julieta Millan , Maria Florencia Acutain , Verónica Báez , Arturo Romano , Mariano Martín Boccia , Feld Mariana

1° Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), UBA-CONICET.
2° Laboratorio de Neurofarmacología de Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica – UBA.
3° Instituto de Biología Celular y Neurociencias Prof. Dr. E. de Robertis (IBCN, CONICET-UBA).

While extensive research has focused on ERK1/2 phosphorylation and its relevance to memory and plasticity, the impact of its dimerization remains largely unexplored. Here, we study the role of ERK2 dimerization on systems with different levels of complexity using native gel electrophoresis, behavioral and pharmacological approach. We assess the ERK2 dimerization level during glycine-induced chemical long-term potentiation (cLTP) in mature rat cortex primary cultures, as well as in mice hippocampus following inhibitory avoidance (IA) memory reactivation. Additionally, we assess the influence of DEL-22379 (DEL), an ERK dimerization inhibitor that doesn’t affect phosphorylation, on IA memory reconsolidation and cLTP.

Our findings reveal that ERK2 dimerization is prompted by cLTP, and this process is suppressed by DEL. We also found that, in this model, DEL is capable of inhibiting both ERK dimerization as well as phosphorylation. Furthermore, reactivating a weak IA memory led to decreased ERK2 dimerization in IA-trained mice, while no changes were found after a strong IA memory reactivation. We also report that when ERK2 dimerization is inhibited after strong IA memory reactivation using DEL, mice behave similar to weak IA-trained mice.

This study is the first to document ERK dimerization in neural tissues and to explore the impact of DEL on memory and plasticity processes. These initial insights underscore the potential role of ERK dimerization in plasticity and memory.