The relative contribution of NMDARs to excitatory postsynaptic currents is controlled by Ca2+-induced inactivation

NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether th...

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Main Authors: Valiullina, Fliza (Author) , Zakharova, Yulia (Author) , Mukhtarov, Marat (Author) , Draguhn, Andreas (Author) , Burnashev, Nail (Author) , Rozov, Andrei (Author)
Format: Article (Journal)
Language:English
Published: 29 January 2016
In: Frontiers in cellular neuroscience
Year: 2016, Volume: 10, Pages: 1-10
ISSN:1662-5102
DOI:10.3389/fncel.2016.00012
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fncel.2016.00012
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fncel.2016.00012/full
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Author Notes:Fliza Valiullina, Yulia Zakharova, Marat Mukhtarov, Andreas Draguhn, Nail Burnashev and Andrei Rozov
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Summary:NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSP) and prolonged the time window for action potential generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons.
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Physical Description:Online Resource
ISSN:1662-5102
DOI:10.3389/fncel.2016.00012