Reduced GluN2A expression induces increased seizure susceptibility in vivo and augmented glutamate sensibility in vitro

ACUTAIN, MARIA FLORENCIA; JERUSALINSKY, DIANA A.; DE OLIVEIRA ALVARES, LUCAS; BAEZ, MARÍA VERÓNICA

Congreso; XXXVI Annual Meeting (SAN 2021); 2021

Sociedad Argentina de Neurociencia (SAN)

Synaptic plasticity involves changes in cytoskeletonproteins and postsynaptic receptors including NMDA receptors (NMDAR). Thesereceptors are heterotetramers composed by two obligatory (GluN1) and tworegulatory subunits, being GluN2A and GluN2B the most expressed in cognitiverelated brain structures. In the last years, grin2A mutations were associated with complex phenotypes that ledto neurodevelopmental disorders which include the occurrence of seizures and insome cases, decreased GluN2A levels. In order to better understand the role ofGluN2A reduced expression in synaptic plasticity and behavior, we induced a GluN2Aknock-down (GluN2A-KD) in two models: primary mature hippocampal neuronalcultures and in the CA1 hippocampal region of young adult Wistar rats. In vivo,the GluN2A KD animals showed increased seizure susceptibility, induced afterPTZ injection. Furthermore, in vitro, the GluN2A-KD neurons showed higherglutamate sensibility than control ones in calcium imaging assays, as well as,changes in dendritic branching and synapse number which were observed byimmunofluorescence. Altogether, these results suggest that GluN2A downregulation, alter glutamate responsiveness and would facilitate seizure outcomethat is a hallmark in patients carrying grin2A mutations