Effects of Chimeric NMDA Receptor GluN2 Subunit Expression on Native NMDA Receptor Pools, Dendritic Morphology, and Synaptic Transmission in the Developing Hippocampus



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The N-methyl-d-aspartate receptor (NMDAR) affects postnatal development of the rodent hippocampus: after the third postnatal week, NMDAR subunit composition shifts from GluN2B to GluN2A, changing both the calcium conductance and intracellular signaling of the NMDAR. It is unknown whether the change in kinetics or protein binding primarily actuate the neurobiological changes that permit mature cognition. Two transgenic mouse lines enable probing of this question: one expresses GluN2A channel domains coupled to the carboxy domain of GluN2B (ABc), while the other expresses GluN2B channel domains coupled to the carboxy domain of GluN2A (BAc). The effects of GluN2 domains on native NMDAR expression, neuron morphology, and synaptic function were examined. Western blotting and immunoprecipitation found that ~30% of native NMDARs are replaced by transgenic NMDARs without increasing total synaptic NMDARs. Dendritic imaging and tracing uncovered increased growth in ABc young adults. Field recordings revealed a higher EPSP amplitude in P22 – P24 ABc synapses. These results illustrate the role of GluN2 domains on late postnatal hippocampal development, providing insight into how GluN2 subunits affect the neurobiological underpinnings of mature learning and memory.



Dendritic Morphology, Development, Electrophysiology, GluN2, Hippocampus, NMDA Receptor