Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses

During cerebellar development, granule cells display well characterized cha nges in the expression of NMDA receptor (NMDAR) NR2 subunits, switching fro m NR2B to NR2A and NR2C in mature cells. Although various studies, includin g experiments on mutant mice with one or more NR2 subunit types deleted, su ggest that NR2A, NR2B, and NR2C subunits contribute to synaptic NMDARs, cha nges in the properties of the mossy fiber EPSC during development have not been fully evaluated. In particular, information on NMDAR EPSCs in mature a nimals is lacking. We have examined pharmacological and kinetic properties of NMDARs at mossy fiber-granule cell synapses from their formation to matu rity [postnatal day 7 (P7)-P40 rats]. Significant changes were seen in the relative amplitudes of the non-NMDAR- and NMDAR-mediated components of the evoked EPSC and in the decay kinetics of the latter. The NMDA/non-NMDA rati o was similar at P7, P21, and P40, but showed a clear peak at P12. This cha nge coincided with a speeding of the NMDAR EPSC decay, accompanied by a dec rease in sensitivity to ifenprodil (selective NR2B-antagonist). By P21, sen sitivity of the NMDAR EPSC to Mg2+ was approximately threefold less than th at at P12 (IC50, 76 vs 28 mu M), suggesting incorporation of the NR2C subun it. However, the predicted slowing of decay kinetics to a value more charac teristic of NR2C deactivation, was not seen until P40. Our data are consist ent with the known switch from NR2B to NR2A subunits during the first two p ostnatal weeks, but suggest a gradual incorporation of the NR2C subunit tha t modifies Mg2+ sensitivity and only later influences EPSC kinetics.