PRESYNAPTIC CONTROL OF SUBUNIT COMPOSITION OF NMDA RECEPTORS MEDIATING SYNAPTIC PLASTICITY

Subunit composition of subsynaptic transmitter receptors is controlled presynaptically in the developing neuromuscular junction. To investig ate presynaptic regulation of NMDA receptor subunit composition in the CNS, we co-cultured different types of hippocampal explants with diss ociated target neurons. Postsynaptic NMDA receptors were studied using whole-cell patch-clamp recordings. After 1 week in culture with inner vation by dentate gyrus (dg) explants, the kinetic and pharmacological properties of postsynaptic NMDA receptors indicated the expression of NMDA receptor subtypes containing NR2B subunits (NR1/NR2A/NR2B or NR1 /NR2B or both). The properties of NMDA receptors in noninnervated neur ons were similar to those of neurons innervated by dg explants. In con trast, after innervation by explants from the cornu ammonis (CA) regio n, we found an additional NMDA receptor subtype with properties consis tent with the subunit composition NR1/NR2A. These findings indicate th at presynaptic signals determine NMDA receptor subunit composition. Af ter prolonged cultivation (11-12 d) the properties of syn aptic NMDA r eceptors in the majority of dg-innervated neurons also indicated the e xpression of NR1/NR2A receptors. This suggests a delayed developmental maturation of NMDA receptors in dg-innervated neurons. Long-term plas ticity of central glutamatergic synapses is critically influenced by t he subunit composition of NMDA receptors, and thus presynaptic control of NMDA receptor subunit composition might regulate synaptic plastici ty.