NMDA receptors (NMDARs) play an important role in synaptic plasticity both in physiological and pathological conditions. GluN2A and GluN2B are the most expressed NMDAR regulatory subunits, in the hippocampus and other cognitive-related brain structures. GluN2B is characteristic of immature structures and GluN2A of mature ones. Changes in GluN2A expression were associated with complex phenotypes that led to complex neurodevelopmental disorders, including the occurrence of seizures. However, little is known about the role of GluN2A in these phenotypes. In this work, we reduced GluN2A expression in mature neuronal cultures and observed an altered GluN2A/GluN2B ratio. Furthermore, those neurons exhibit an increase in immature dendritic spines and dendritic branching, as well as an increased response to glutamate stimulus. This phenotype (considering GluN2A/GluN2B ratio, index branching and glutamate response) resembles those observed at immature neuronal stages in vitro. We propose that this immature phenotype led to a higher response to glutamate stimulus which, in vivo, would be the basis of reduced threshold for seizure onset in GluN2A-pathological conditions.
© 2023 International Society for Neurochemistry.