Presynaptic exocytosis regulates NR2A mRNA expression in cultured neocortical neurones

N-methyl-D-aspartate (NMDA) receptors are hetero-oligomeric receptor-channel complexes composed of NR1 and NR2 subunits. Subunit composition determines the properties of NMDA receptor subtypes. However, the molecular mechanisms regulating their subunit composition are unknown. Using reverse transcription (RT)-competitive PCR we studied the expression of NR2A and NR2B mRNA in neocortical neurones differentiating in culture. We found a developmental increase in NR2A mRNA expression in relation to NR2B mRNA expression. This increase was inhibited by addition of tetanus toxin to the culture medium and by chronic pharmacological blockade of postsynaptic, ionotropic glutamate receptors. These results suggest that presynaptic exocytosis regulates NR2A mRNA expression. This mechanism might influence NMDA receptor properties and thus developmental changes in long-term synaptic plasticity.