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

Deniz Atasoy; Mert Ertunc; Krista L Moulder; Justin Blackwell; ChiHye Chung; Jianzhong Su; Ege T Kavalali

doi:10.1523/JNEUROSCI.2432-08.2008

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

Journal article

Open access

Peer reviewed

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

Deniz Atasoy, Mert Ertunc, Krista L Moulder, Justin Blackwell, ChiHye Chung, Jianzhong Su and Ege T Kavalali

The Journal of neuroscience, Vol.28(40), pp.10151-10166

10/01/2008

DOI: 10.1523/JNEUROSCI.2432-08.2008

PMCID: PMC2578837

PMID: 18829973

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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 approximately 0.2 microm(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.

Animals, Newborn

Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors

Cells, Cultured

Receptors, N-Methyl-D-Aspartate - metabolism

Rats

Excitatory Amino Acid Agonists - pharmacology

Excitatory Amino Acid Antagonists - pharmacology

Excitatory Postsynaptic Potentials - drug effects

Rats, Sprague-Dawley

Receptor Cross-Talk - physiology

Excitatory Postsynaptic Potentials - physiology

Animals

Receptors, N-Methyl-D-Aspartate - agonists

Glutamic Acid - secretion

Receptor Cross-Talk - drug effects

Details

Title: Subtitle: Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap
Creators: Deniz Atasoy - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA
Mert Ertunc
Krista L Moulder
Justin Blackwell
ChiHye Chung
Jianzhong Su
Ege T Kavalali
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.28(40), pp.10151-10166
Publisher: United States
DOI: 10.1523/JNEUROSCI.2432-08.2008
PMID: 18829973
PMCID: PMC2578837
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: MH052804 / NIMH NIH HHS R01 MH066198-05 / NIMH NIH HHS DA018109 / NIDA NIH HHS K01 DA018109 / NIDA NIH HHS R01 MH068437 / NIMH NIH HHS R37 MH052804 / NIMH NIH HHS R01 MH068437-05 / NIMH NIH HHS R01 MH066198 / NIMH NIH HHS
Language: English
Date published: 10/01/2008
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040392402771

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