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NMDA Receptor Activation by Spontaneous Glutamatergic Neurotransmission
- Source :
- Journal of Neurophysiology. 101:2290-2296
- Publication Year :
- 2009
- Publisher :
- American Physiological Society, 2009.
-
Abstract
- Under physiological conditions N-methyl-d-aspartate (NMDA) receptor activation requires coincidence of presynaptic glutamate release and postsynaptic depolarization due to the voltage-dependent block of these receptors by extracellular Mg2+. Therefore spontaneous neurotransmission in the absence of action potential firing is not expected to lead to significant NMDA receptor activation. Here we tested this assumption in layer IV neurons in neocortex at their resting membrane potential (approximately −67 mV). In long-duration stable recordings, we averaged a large number of miniature excitatory postsynaptic currents (mEPSCs, >100) before or after application of dl-2 amino 5-phosphonovaleric acid, a specific blocker of NMDA receptors. The difference between the two mEPSC waveforms showed that the NMDA current component comprises ∼20% of the charge transfer during an average mEPSC detected at rest. Importantly, the contribution of the NMDA component was markedly enhanced at membrane potentials expected for the depolarized up states (approximately −50 mV) that cortical neurons show during slow oscillations in vivo. In addition, partial block of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor component of the mEPSCs did not cause a significant reduction in the NMDA component, indicating that potential AMPA receptor-driven local depolarizations did not drive NMDA receptor activity at rest. Collectively these results indicate that NMDA receptors significantly contribute to signaling at rest in the absence of dendritic depolarizations or concomitant AMPA receptor activity.
- Subjects :
- Patch-Clamp Techniques
Time Factors
Physiology
Biophysics
Glutamic Acid
Neocortex
Kainate receptor
AMPA receptor
In Vitro Techniques
Neurotransmission
Receptors, N-Methyl-D-Aspartate
Rats, Sprague-Dawley
Glutamatergic
Postsynaptic potential
Animals
Long-term depression
Neurons
Analysis of Variance
Chemistry
General Neuroscience
Miniature Postsynaptic Potentials
Excitatory Postsynaptic Potentials
Valine
Articles
Electric Stimulation
Rats
Animals, Newborn
nervous system
Excitatory postsynaptic potential
NMDA receptor
Excitatory Amino Acid Antagonists
Neuroscience
Subjects
Details
- ISSN :
- 15221598 and 00223077
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Journal of Neurophysiology
- Accession number :
- edsair.doi.dedup.....0794369280815c8c64e630daa536ced2