CONICET | Buscador de Institutos y Recursos Humanos

It is well recognized that the NMDA receptors(NMDAR) are involved in synaptic plasticity, learning processes and memory, buttheir specific regulation is little known. NMDAR are composed by two GluN1obligatory subunits and two regulatory subunits: GluN2 (A-D) or GluN3 (A-B). GluN2Aand GluN2B are the most expressed regulatory subunits in hippocampus and othermemory related brain structures, where GluN2A and GluN2B transcription andtranslation are tightly regulated. This results in GluN2B expression inimmature synapses, and GluN2A in mature and stable synapses. In order tounderstand the role of GluN2A during memory acquisition and plasticity inductionwe built two AAV-eGFP vectors: one of them codifying a shRNA anti GluN2A(AAV-sh2A), and the other carrying a shRNA scramble as control (AAV-shSc). Weinfected mature primary neuronal cultures with AAV-sh2A or AAV-shSc andanalyzed not only the specificity of GluN2A knockdown but also the effects ofthis decrease on other synaptic protein expression: Synapsin-1 and PSD95. Aswas expected, we observed by qPCR, a decrease in GluN2A mRNA only in primarycultures infected with AAVsh2A, without changes in GluN1 or GluN2B expression. Interestinglyin those cultures, GluN2A decreased expression was accompanied by a significantdiminution on GluN1 protein level. Furthermore, GluN2B levels were similar tocontrol cultures infected with the AAV-shSc. On the other hand, we found anincreased expression of Synapsin-1 and PSD95 in GluN2A knockdown cultures. Theseresults, suggest that although GluN2A decrease does not change NMDAR subunitexpression at transcriptional level, it could activate some postranscriptionalregulatory mechanisms that change GluN1 protein levels. Moreover, that changeseems to induce a rise in the synapsis without NMDARs increase.