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The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca2+-Induced Inactivation

Abstract : NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca 2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca 2+ concentration. It is unclear however, whether the Ca 2+ 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 neuronal 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 Ca 2+ buffers. Loading of pyramidal cells with exogenous Ca 2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca 2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg 2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca 2+ buffer capacity of postsynaptic neurons.
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Submitted on : Friday, May 4, 2018 - 11:55:18 AM
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Fliza Valiullina, Yulia Zakharova, Marat Mukhtarov, Andreas Draguhn, Nail Burnashev, et al.. The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca2+-Induced Inactivation. Frontiers in Cellular Neuroscience, Frontiers, 2016, 10, pp.12 - 12. ⟨10.3389/fncel.2016.00012⟩. ⟨hal-01785333⟩



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