Fig. 1
CT100(I716F)-mediated synaptic depression in granule cells of adult mice is NMDAR dependent. a Double infection with rAAV-Syn-Cre-T2A-GFP and rAAV-CaMKII-CT100(I716F)-T2A-tdTomato in DG neurons. The arrowhead points to a double-infected DG granule cell. b pAAV constructs were used to express CT100(I716F) or Cre-recombinase or tdTomato as control. c Example traces of mEPSC recordings from GluN1fl/fl mice injected with the different AAV constructs as indicated. d + e CT100(I716F) increases inter-event-interval (IEI) and reduces mEPSC frequency in DG granule cells in cells of GluN1fl/fl mice. Deletion of GluN1 (GluN1−/−) increases mEPSC frequency. Overexpression of CT100(I716F) does not significantly reduce mEPSC frequency in GluN1−/− granule cells. f To test if the effect of CT100(I716F) in GluN1fl/fl neurons is different from that in GluN1−/− granule cells, we calculated the respective percent of CT100(I716F)-mediated reduction in mEPSC frequency. The mEPSC frequency is smaller in GluN1fl/fl/CT100(I716F) than in GluN1fl/fl cells (blue bar) and slightly bigger in GluN1−/−/CT100(I716F) than in GluN1−/− cells (gray bar). The reduction in GluN1fl/fl cells is significantly bigger than the effect of CT100(I716F) in GluN1−/− granule cells. g + h CT100(I716F) reduces mEPSC frequency in DG granule cells in cells of GluN2Afl/fl mice, but does not significantly reduce mEPSC frequency in GluN2A−/− granule cells. i The CT100(I716F)-mediated decrease in mEPSC frequency in GluN2Afl/fl cells is not significantly different from the decrease in GluN2A−/− cells. j + k CT100(I716F) increases IEI and reduces mEPSC frequency in DG granule cells of GluN2Bfl/fl mice. Deletion of GluN2B (GluN2B−/−) increases mEPSC frequency. Overexpression of CT100(I716F) does not significantly reduce mEPSC frequency in GluN2B−/− granule cells. l The CT100(I716F)-mediated decrease in mEPSC frequency in GluN2Bfl/fl cells is not significantly different from the decrease in GluN2B−/− cells. m Example traces of paired-pulse recordings (PPR) with pairs of inter-stimulus intervals (ISI) of 25 ms n The PPR of the amplitudes of two currents evoked with 25 ms or 50 ms ISIs is not different in control cells and CT100(I716F)-overexpressing cells. ISIs are shown on the top of the quantification. Bar graphs show median ± IQR. * = p < 0.05, ** = p < 0.01, *** = p < 0.001; cum. = cumulative