IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
GluN2A KD alters neuronal synaptic plasticity in neuronal mature cultures
Autor/es:
JERUSALINSKY, DIANA A.; ACUTAIN, M. FLORENCIA; SALVETTI, ANNA; VAZQUEZ, CECILIA ALEJANDRA; BAEZ M. VERÓNICA
Lugar:
Montreal
Reunión:
Congreso; ISN-ASN Meeting 2019; 2019
Institución organizadora:
International Society for Neurochemistry-American Society for Neurochemistry
Resumen:
Synaptic plasticity refers to long lasting changes in synapses that have been related to the structural bases of memory and learning processes. For several years, NMDA receptors (NMDAR) have been involved in those processes as well as in several neuropathologies. NMDAR are composed by two GluN1 obligatory subunits and two regulatory subunits: GluN2 (A-D) or GluN3 (A-B). In cognitive related brain structures GluN2A and GluN2B are the most expressed regulatory subunits, that undergo a tightly regulation. Whereas GluN2B expression is characteristic of immature synapses, GluN2A is present in mature synapses. In order to better understand the role of GluN2A in synapsis, we transduced mature neuronal cultures with AAV-eGFP vectors: one codifying a specific shRNA anti GluN2A, AAV-sh2A, and the other carrying a shRNA scramble as control, AAV-shSc. We verified that AAV-sh2A knocks down GluN2A mRNA and protein levels (GluN2A KD). Moreover we evaluated neuronal morphology and two synaptic proteins: Syn-1 and PSD95. In GluN2A KD cultures we confirmed the increase in dendritic arbor complexity observed previously. Interestingly, in those cultures we found a significant decrease in GluN1 protein, while GluN2B protein levels did not change. Furthermore, in those cultures the expression of Syn-1 and PSD95 was increased, which suggest that synaptic function was altered. For these reason we analyzed GluN2A KD cultures by Ca+2 imaging and observed changes in the excitability of neurons after chemical LTP. These results suggest that GluN2A KD induce a rearrangement of NMDAR expression that modifies synaptic physiology