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

Research output: Contribution to journalArticle

110 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)10151-10166
Number of pages16
JournalJournal of Neuroscience
Volume28
Issue number40
DOIs
StatePublished - Oct 1 2008

Fingerprint

N-Methyl-D-Aspartate Receptors
Glutamic Acid
Dizocilpine Maleate
Population
Synapses
Post-Synaptic Density
Imines
Synaptic Vesicles
Optical Imaging
Glutamate Receptors
N-Methylaspartate
Synaptic Transmission
Action Potentials
Neurotransmitter Agents

Keywords

  • Neurotransmission
  • NMDA receptor
  • Synapse
  • Synaptic communication
  • Synaptic plasticity
  • Synaptic transmission
  • Synaptic vesicle release

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap. / Atasoy, Deniz; Ertunc, Mert; Moulder, Krista L.; Blackwell, Justin; Chung, Chihye; Su, Jianzhong; Kavalali, Ege T.

In: Journal of Neuroscience, Vol. 28, No. 40, 01.10.2008, p. 10151-10166.

Research output: Contribution to journalArticle

Atasoy, Deniz ; Ertunc, Mert ; Moulder, Krista L. ; Blackwell, Justin ; Chung, Chihye ; Su, Jianzhong ; Kavalali, Ege T. / Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 40. pp. 10151-10166.
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