Selective modulation of AMPAR-mediated transmission in 4E-BP2−/− mice.

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Selective modulation of AMPAR-mediated transmission in 4E-BP2−/− mice. Selective modulation of AMPAR-mediated transmission in 4E-BP2−/− mice. A, Examples of EPSCs composed of AMPAR and NMDAR-mediated components. Arrows indicate points at which amplitude of AMPAR and NMDAR components was measured at holding potentials of −70 mV and +40 mV, respectively. Note the increase in the AMPAR-mediated component and unchanged NMDAR component in the cell from 4E-BP2−/− mice. Arrowhead indicates time of stimulation. B, Summary bar graph showing the increase in AMPAR/NMDAR EPSC ratio in 4E-BP2−/− mice. Data are mean ± SEM. *p < 0.05. C–D, Representative traces (C) and mean current–voltage relations (D) of NMDAR-mediated EPSCs recorded at different holding potentials in the presence of the AMPAR antagonist DNQX, showing intact amplitude and voltage–current relation of NMDAR-mediated EPSCs in cells of 4E-BP2−/− mice. E, Decrease in the proportion of silent synapses in 4E-BP2−/− mice. Left, Example of EPSCs at AMPAR silent synapse in a cell from wild-type mice (WT). NMDAR-mediated EPSCs were evoked at +40 mV holding potential, and no AMPAR-mediated EPSC was detected at −60 mV. Example of EPSCs from a cell from 4E-BP2−/− mice (4E-BP2−/−) with both NMDAR and AMPAR-mediated components. Right, Summary plot of proportion (expressed as percentage total) of cells with AMPAR silent or functional synapses, showing reduced incidence of silent synapses in 4E-BP2−/− mice. F, No change in current–voltage relation of AMPAR-mediated EPSCs in 4E-BP2−/− mice. Left, Representative traces (average of 30 events) showing AMPAR-mediated EPSCs (stimulation intensity, 2 × threshold) recorded in ACSF containing AP5 (50 μm) and gabazine (5 μm) to block NMDA and GABA receptors, respectively. EPSCs were evoked at different membrane potentials (−70, 0, and +40 mV) in CA1 pyramidal neurons from wild-type (left traces, black) and 4E-BP2−/− mice (right traces, gray). Right, Summary current–voltage plots for all cells showing unchanged linear voltage–current relation in 4E-BP2−/− mice. Israeli Ran et al. J. Neurosci. 2013;33:1872-1886 ©2013 by Society for Neuroscience