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J. Neurosci. 28 (40): 10151-10166

Copyright © 2008 by the Society for Neuroscience.


Cellular/Molecular

Spontaneous and Evoked Glutamate Release Activates Two Populations of NMDA Receptors with Limited Overlap

Deniz Atasoy,1 Mert Ertunc,1 Krista L. Moulder,3 Justin Blackwell,4 ChiHye Chung,1 Jianzhong Su,4 , and Ege T. Kavalali1,2

Departments of 1Neuroscience and 2Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, 3Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, and 4Department of Mathematics, University of Texas at Arlington, Arlington, Texas 76019-0408

Correspondence should be addressed to Dr. Ege T. Kavalali, Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111. Email: Ege.Kavalali{at}UTSouthwestern.edu

Abstract: 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 ~0.2 µm2 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.

Key Words: synaptic vesicle release • synaptic transmission • synaptic communication • synapse • NMDA receptor • synaptic plasticity • neurotransmission


Received for publication May 30, 2008. Revision received July 26, 2008. Accepted for publication Aug. 20, 2008.

Correspondence should be addressed to Dr. Ege T. Kavalali, Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111. Email: Ege.Kavalali{at}UTSouthwestern.edu


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