Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap

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Atasoy D., Ertunc M., Moulder K. L., Blackwell J., Chung C., Su J., ...More

JOURNAL OF NEUROSCIENCE, vol.28, no.40, pp.10151-10166, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 40
  • Publication Date: 2008
  • Doi Number: 10.1523/jneurosci.2432-08.2008
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.10151-10166
  • Keywords: synaptic vesicle release, synaptic transmission, synaptic communication, synapse, NMDA receptor, synaptic plasticity, neurotransmission, METHYL-D-ASPARTATE, SYNAPTIC-TRANSMISSION, TRANSMITTER RELEASE, PYRAMIDAL NEURONS, NONUNIFORM PROBABILITY, ASYNCHRONOUS RELEASE, CALCIUM TRANSIENTS, QUANTAL RELEASE, SYNAPTOTAGMIN-I, GRANULE CELLS
  • Hacettepe University Affiliated: No


In a synapse, spontaneous and action-potential-driven neurotransmitter release is assumed to activate the same set of postsynaptic receptors. Here, we tested this assumption using (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), a well characterized use-dependent blocker of NMDA receptors. NMDA-receptor-mediated spontaneous miniature EPSCs (NMDA-mEPSCs) were substantially decreased by MK-801 within 2 min in a use-dependent manner. In contrast, MK-801 application at rest for 10 min did not significantly impair the subsequent NMDA-receptor-mediated evoked EPSCs (NMDA-eEPSCs). Brief stimulation in the presence of MK-801 significantly depressed evoked NMDA-eEPSCs but only mildly affected the spontaneous NMDA-mEPSCs detected on the same cell. Optical imaging of synaptic vesicle fusion showed that spontaneous and evoked release could occur at the same synapse albeit without correlation between their kinetics. In addition, modeling glutamate diffusion and NMDA receptor activation revealed that postsynaptic densities larger than similar to 0.2 mu m(2) can accommodate two populations of NMDA receptors with nonoverlapping responsiveness. Collectively, these results support the premise that spontaneous and evoked neurotransmissions activate distinct sets of NMDA receptors and signal independently to the postsynaptic side.