Deletion of the NMDA receptor GluN2A subunit significantly decreases dendritic growth in maturing dentate granule neurons.

Abstract

It is known that NMDA receptors can modulate adult hippocampal neurogenesis, but the contribution of specific regulatory GluN2 subunits has been difficult to determine. Here we demonstrate that mice lacking GluN2A (formerly NR2A) do not show altered cell proliferation or neuronal differentiation, but present significant changes in neuronal morphology in dentate granule cells. Specifically, GluN2A deletion significantly decreased total dendritic length and dendritic complexity in DG neurons located in the inner granular zone. Furthermore, the absence of GluN2A also resulted in a localized increase in spine density in the middle molecular layer, a region innervated by the medial perforant path. Interestingly, alterations in dendritic morphology and spine density were never seen in dentate granule cells located in the outer granular zone, a region that has been hypothesized to contain older, more mature, neurons. These results indicate that although the GluN2A subunit is not critical for the cell proliferation and differentiation stages of the neurogenic process, it does appear to play a role in establishing synaptic and dendritic morphology in maturing dentate granule cells localized in the inner granular zone.