title: The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca(2+)-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.
authors: OpenLab of Neurobiology, Kazan Federal University Kazan, Russia.
authors: Fliza
authors: F
authors: Valiullina
authors: OpenLab of Neurobiology, Kazan Federal University Kazan, Russia.
authors: Yulia
authors: Y
authors: Zakharova
authors: OpenLab of Neurobiology, Kazan Federal University Kazan, Russia.
authors: Marat
authors: M
authors: Mukhtarov
authors: Department of Physiology and Pathophysiology, University of Heidelberg Heidelberg, Germany.
authors: Andreas
authors: A
authors: Draguhn
authors: INMED, Institut de Neurobiologie de la Méditerranée UMR901, Aix-Marseille UniversitéMarseille, France; INSERM U901Marseille, France.
authors: Nail
authors: N
authors: Burnashev
authors: OpenLab of Neurobiology, Kazan Federal UniversityKazan, Russia; Department of Physiology and Pathophysiology, University of HeidelbergHeidelberg, Germany.
authors: Andrei
authors: A
authors: Rozov
keywords: NMDA receptor; action potentials; calcium; excitation; firing properties; modulation