A dual mechanism for impairment of GABA A receptor activity by NMDA receptor activation in rat cerebellum granule cells

1997 ◽  
Vol 25 (3) ◽  
pp. 181-187 ◽  
Author(s):  
M. Robello ◽  
C. Amico ◽  
A. Cupello
Keyword(s):  
Nmda Receptor ◽  
Granule Cells ◽  
Receptor Activation ◽  
Receptor Activity ◽  
Gaba A ◽  
Rat Cerebellum ◽  
Dual Mechanism ◽  
Nmda Receptor Activation

scholarly journals NMDA Receptor Activation by Spontaneous Glutamatergic Neurotransmission

2009 ◽  
Vol 101 (5) ◽  
pp. 2290-2296 ◽  
Author(s):  
Felipe Espinosa ◽  
Ege T. Kavalali
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ampa Receptor ◽  
Cortical Neurons ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Receptor Activity ◽  
Resting Membrane Potential ◽  
Nmda Current ◽  
Nmda Receptor Activation

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.

scholarly journals Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation

2002 ◽  
Vol 67 (6) ◽  
pp. 2484-2493 ◽  
Author(s):  
Emanuela Bonfoco ◽  
Marcel Leist ◽  
Boris Zhivotovsky ◽  
Sten Orrenius ◽  
Stuart A. Lipton ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Receptor Activation ◽  
No Donors ◽  
Cerebellar Granule ◽  
Nmda Receptor Activation

Endogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons

1998 ◽  
Vol 80 (1) ◽  
pp. 196-208 ◽  
Author(s):  
Antoine Robert ◽  
Joel A. Black ◽  
Stephen G. Waxman
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Single Channel ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Receptor Activity ◽  
Spinal Neurons ◽  
Quantal Size ◽  
Endogenous Activity ◽  
Nmda Receptor Activation

Robert, Antoine, Joel A. Black, and Stephen G. Waxman. Endogenous NMDA-receptor activation regulates glutamate release in cultured spinal neurons. J. Neurophysiol. 80: 196–208, 1998. N-methyl-d-aspartate (NMDA) receptor activation plays a fundamental role in the genesis of electrical activity of immature neurons and may participate in activity-dependent aspects of CNS development. A recent study has suggested that NMDA-receptor–mediated glutamatergic neurotransmission might occur in the developing spinal cord via activation of nonsynaptic receptors, but the details of NMDA-receptor activation in the developing CNS are not yet well understood. We describe here a model of cultured spinal neurons that display ongoing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity characterized by spontaneous excitatory postsynaptic currents (EPSCs), with NMDA-receptor activity detectable only as single channel events. dl-2-amino-5-phosphonovaleric acid (100 μM) and tetrodotoxin (TTX) 100 nM each reduced the occurrence of spontaneous AMPA EPSCs; quantal analysis showed a decrease in the number of released quanta but no changes in quantal size, indicating that NMDA-receptor activation and Na+ channel activity affect the generation of spontaneous AMPA EPSCs, at least in part, via mechanisms that impinge on the presynaptic terminal. Once the Mg2+-block was released, activity of NMDA receptors dramatically increased the release of quantal and multiquantal amounts of glutamate, indicating that the NMDA receptors are physiologically coupled to glutamate release. In Mg2+-free solution, TTX application elicited an increase in the number of quantal AMPA EPSCs and a reduction in the number of multiquantal EPSCs, consistent with an effect of NMDA-receptor activation on presynaptic terminals. Our results suggest that endogenous activity at a small number of NMDA receptors can regulate the release of neurotransmitters at developing AMPA synapses.

d-Serine regulates CREB phosphorylation induced by NMDA receptor activation in Müller glia from the retina

2007 ◽  
Vol 427 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Mónica Lamas ◽  
Irene Lee-Rivera ◽  
Mónica Ramírez ◽  
Ana María López-Colomé
Keyword(s):  
Nmda Receptor ◽  
Receptor Activation ◽  
Muller Glia ◽  
Müller Glia ◽  
Creb Phosphorylation ◽  
Nmda Receptor Activation
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