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Volume 17, Number 8, Issue of April 15, 1997 pp. 2766-2774
Copyright ©1997 Society for NeurosciencePresynaptic Control of Subunit Composition of NMDA Receptors Mediating Synaptic Plasticity
Received Nov. 27, 1996; revised Jan. 21, 1997; accepted Jan. 30, 1997.
Kurt Gottmann, Alexander Mehrle, Günter Gisselmann, and Hanns Hatt Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, 44780 Bochum, Germany
Subunit composition of subsynaptic transmitter receptors is controlled presynaptically in the developing neuromuscular junction. To investigate presynaptic regulation of NMDA receptor subunit composition in the CNS, we co-cultured different types of hippocampal explants with dissociated target neurons. Postsynaptic NMDA receptors were studied using whole-cell patch-clamp recordings.
After 1 week in culture with innervation 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 neurons were similar to those of neurons innervated by dg explants. In contrast, after innervation by explants from the cornu ammonis (CA) region, we found an additional NMDA receptor subtype with properties consistent with the subunit composition NR1/NR2A. These findings indicate that presynaptic signals determine NMDA receptor subunit composition.
After prolonged cultivation (11-12 d) the properties of synaptic NMDA receptors in the majority of dg-innervated neurons also indicated the expression of NR1/NR2A receptors. This suggests a delayed developmental maturation of NMDA receptors in dg-innervated neurons.
Long-term plasticity of central glutamatergic synapses is critically influenced by the subunit composition of NMDA receptors, and thus presynaptic control of NMDA receptor subunit composition might regulate synaptic plasticity.
Key words: hippocampal cells; developmental maturation; NMDA receptors; synaptic transmission; patch clamp; single-cell RT-PCR
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