The role of NMDA receptor NR2 subunit in synaptogenesis and synaptic stabilization

The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in establishing, maintaining, and modifying glutamatergic synapses in the hippocampus. I used a combination of molecular biology, electrophysiology, and imaging techniques to show that the subunit composition of this receptor, and specifically the type of NR2 subunit it contains, are critical for determining how the NMDAR can adjust the sensitivity of the synapse to changes in the frequency of stimulation, how specific synapses are functionally and structurally stabilized, and how lateral movements of the receptor in the plasma membrane can result in recovery of NMDAR-mediated current following pharmacological blockade. Specifically, I found that NR2B-containing NMDARs enter the synapse after a period of low or null synaptic stimulation; that NR2B-containing receptors are required for the proper number of synapses to develop; that NR2A-containing receptors can act to structurally stabilize a synapse and the dendritic spine; that the functions of the NMDAR that mediate structural plasticity are mediated through interaction in the intracellular C-terminus; and that rapid lateral movements of the NMDAR may be a way for NMDARs to enter the synapse following blockade with MK801.