Figure 4. NMDAR transmission dysfunction at motor cortex to DLS MSN in YAC128 mice. A, left, Experimental schematic. Left down, In vitro validation of 20-Hz blue light stimulation protocol. Scale bar: 0.1 s, 10 mV. Right, Epifluorescent image of AAV5-CamKII-hChR2(H134R)-EGFP injection in the thalamus (top) or in the motor cortex (down). B, C, Group mean AMPA/NMDAR ratio calculated in WT and YAC128 MSN at thalamo-dorsolateral synapses (B) or at motor cortex to dorsolateral synapses (C). Right, Example traces of evoked AMPAR- and NMDAR-EPSCs at +40 mV. Scale bar: 50 ms, 25 pA (B) and 10 ms, 50 pA (C). D, Group mean AMPA/NMDAR ratio calculated in WT-D1+ MSN, WT-D1– MSN, YAC128-D1+ MSN and YAC128-D1– MSN at motor cortex to dorsolateral synapses. Scale bar: 10 ms, 50 pA. E, Group mean RI calculated at motor cortex to DLS synapses in WT and YAC128 MSN. Right, Example traces of evoked AMPAR-EPSCs recorded at −60, 0, and +40 mV. Scale bar: 10 ms, 50 pA (for YAC128) and 10 ms, 50 pA (for WT). F, I-O relationship of motor cortex glutamatergic transmission established by the stimulation duration (synaptic input) and the amplitude of the EPSC (output) in slices from WT and YAC128 MSN. Right, Representative EPSCs evoked by motor cortex terminal stimulation in DLS recorded at −60 mV in WT and YAC128 MSN. Scale bar: 10 ms, 50 pA. G, Group mean amplitude of asynchronous evoked events in WT and YAC128 MSN. Right, Example traces of evoked AMPAR-aEPSCs recorded at –70 mV. Star indicating an asynchronous event detected. Scale bar: 50 ms, 25 pA. H, Group mean decay time of NMDAR–EPSCs at +40 mV in WT and YAC128 MSN. Right, Example traces of NMDAR-EPSC at +40 mV. I, Time course of NMDAR-EPSC amplitude during ifenprodil application for WT and YAC128 MSN. Scale bar: 15 ms. J, Group mean ifenprodil inhibition calculated in WT and YAC128 MSN. Right, Example traces of NMDAR-EPSCs during ifenprodil (3 μM) bath application. Scale bar: 20 ms, 25 pA. K, I-V plots of normalized and averaged NMDAR-EPSCs of motor cortex to DLS MSN in WT and YAC128 mice and their associated example traces. Scale bar: 50 ms, 50 pA. L, Group mean PPR recorded at interval of 50, 100, and 300 ms for WT and YAC128 MSN evoked by motor cortex stimulation. Right, Example traces of AMPAR-EPSC at −60 mV in WT and YAC128 MSN. Scale bar: 50 ms, 25 pA. Square symbols represent female mice and circles represent males.