Development of NMDA NR2 subunits and their roles in critical period maturation of neocortical GABAergic interneurons.

The goals of this research are to (1) determine the changes in the composition of NMDA receptor (NMDAR) subunits in GABAergic interneurons during critical period (CP); and (2) test the effect of chronic blockage of specific NR2 subunits on the maturation of specific GABAergic interneurons. Our data demonstrate that: (1) The amplitude of NMDAR mediated EPSCs (EPSCs(NMDAR) ) was significantly larger in the postCP group. (2) The coefficient of variation (CV), τ(decay) and half-width of EPSCs(NMDAR) were significantly larger in the preCP group. (3) A leftward shift in the half-activation voltages in the postCP vs. preCP group. (4) Using subunit-specific antagonists, we found a postnatal shift in NR2 composition towards more NR2A mediated EPSCs(NMDAR) . These changes occurred within a two-day narrow window of CP and were similar between fast-spiking (FS) and regular spiking (RSNP) interneurons. (5) Chronic blockage of NR2A, but not NR2B, decreased the expression of parvalbumin (PV), but not other calcium binding proteins in layer 2/3 and 4 of barrel cortex. (6) Chronic blockage of NR2A selectively affected the maturation of IPSCs mediated by FS cells. In summary, we have reported, for the first time, developmental changes in the molecular composition of NMDA NR2 subunits in interneurons during CP, and the effects of chronic blockage of NR2A but not NR2B on PV expression and inhibitory synaptic transmission from FS cells. These results support an important role of NR2A subunits in developmental plasticity of fast-spiking GABAergic circuits during CP.