N-methyl-D-aspartate receptors (NMDARs) are glutamatergic receptors that take part in excitatory synaptic transmission and drive functional and structural neuronal plasticity, including activity-dependent changes in dendritic morphology. Forebrain NMDARs contribute to neuronal plasticity in at least two ways: through calcium-mediated processes or via direct intracellular postsynaptic signaling. Both properties are regulated by the GluN2 subunits. However, the separate contributions of these properties to the regulation of dendritic morphology are unknown. We created transgenic mice that express chimeric GluN2 subunits and examined the impact on pyramidal cell dendritic morphology in hippocampal region CA1. Golgi-Cox impregnation and transgenic expression of green fluorescent protein were employed to visualize dendritic arbors. In adult mice with a predominantly native GluN2A background, overexpression of the GluN2B carboxy terminus increased the total path of the dendritic arbor without affecting branch number or tortuosity. Overexpressing the amino terminus and transmembrane domains of GluN2B had little effect. It may be inferred from these results that NMDAR-dependent intracellular signaling regulates dendritic morphology of hippocampal pyramidal cells more so than calcium conductance dynamics. The findings add to the understanding of NMDAR-mediated signaling in hippocampal neurons and support re-investigation of the molecular underpinnings of NMDAR involvement in postnatal dendrite maturation.

N‐methyl‐D‐aspartate receptors (NMDARs) can be considered to be the de facto “plasticity” receptors in the brain due to their central role in the activity‐dependent modification of neuronal morphology and synaptic transmission. Since the 1980s, research on NMDARs has focused on the second messenger properties of calcium and the downstream signaling pathways that mediate alterations in neural form and function. Recently, NMDARs were shown to drive activity‐dependent synaptic plasticity without calcium influx. How this “nonionotropic” plasticity occurs in vitro is becoming clearer, but research on its involvement in behavior and cognition is in its infancy. There is a partial overlap in the downstream signaling molecules that are involved in ionotropic and nonionotropic NMDAR‐dependent plasticity. Given this, and prior studies of the cognitive impacts of ionotropic NMDAR plasticity, a preliminary model explaining how NMDAR nonionotropic plasticity affects learning and memory can be established. We hypothesize that nonionotropic NMDAR plasticity takes part in latent memory encoding in immature rodents through nonassociative depression of synaptic efficacy, and possibly shrinking of dendritic spines. Further, the late postnatal alteration in NMDAR composition in the hippocampus appears to reduce nonionotropic signaling and remove a restriction on memory retrieval. This framework substantially alters the canonical model of NMDAR involvement in spatial cognition and hippocampal maturation and provides novel and exciting inroads for future studies.