Reduced expression of GluN2A induces a delay in neuron maturation in primary neuronal cultures

ACUTAIN, MARIA FLORENCIA; BAEZ, MARÍA VERÓNICA

Congreso; SAN2023 Annual Meeting; 2023

Sociedad Argentina de Neurociencia

NMDA receptors (NMDARs) play an important role in synaptic plasticity both inphysiological and pathological conditions. GluN2A and GluN2B are the most expressedNMDAR regulatory subunits, in the hippocampus and other cognitive-related brainstructures. GluN2B is characteristic of immature structures and GluN2A of mature ones.Changes in GluN2A expression were associated with complex phenotypes that led tocomplex neurodevelopmental disorders, including the occurrence of seizures. However,little is known about the role of GluN2A in these phenotypes. In this work, we reducedGluN2A expression in mature neuronal cultures and observed an altered GluN2A/GluN2Bratio. Furthermore, those neurons exhibit an increase in immature dendritic spines anddendritic branching, as well as increased response to glutamate stimulus. Thisphenotype (considering GluN2A/GluN2B ratio, index branching and glutamate response)resembles those observed at immature neuronal stages in vitro. This immaturephenotype led to a higher response to glutamate stimulus which, in vivo, would be thebasis of reduced threshold for seizure-onset in GluN2A-pathological conditions