Neocortical synaptic LTD. A, Electrical 5 Hz stimulation (arrow) induces LTD of EPSPs. This form of synaptic plasticity is associated with a decrease in the dendritic glutamate sensitivity. To 6 of the 14 neurons, the 5 Hz train of light flashes (arrow with flash symbol) was applied. No additional photo-LTD could be elicited in these neurons (gray diamonds), indicating a complete occlusion of photo-LTD by synaptic LTD. Without LTD induction, the glutamate response was stable for the entire time of recording (60 min, white squares). Thedashed line represents the 100% value. B, Traces of glutamate responses and EPSPs before and 35 min after electrical 5 Hz stimulation. Depolarizations elicited by photostimulation had a time-to-peak (62 ± 3 msec) that was approximately three times as long as the time-to- peak of electrically evoked EPSPs (20 ± 2 msec; n = 7 neurons).C, Comparison of the reduction in EPSP amplitude (white bar) and glutamate response peak (black bar) during synaptic LTD. Forty-eight minutes after electrical LTD induction, both potentials show no difference (p > 0.5). The gray barindicates the mean reduction in the glutamate response amplitude of the neurons, which were also stimulated by a 5 Hz light tetanus.D, Photo-LTD and synaptic LTD are not associated with a change in the glutamate response kinetics. Traces show single glutamate responses before and after the 5 Hz stimulation. The unchanged kinetics of the glutamate responses is clearly recognizable if the sweeps are scaled. c, Control.E, Synaptic LTD is NMDA receptor dependent. Blockade of NMDA receptors by MK801 and a high extracellular Mg2+ concentration prevented the induction of synaptic LTD and the decrease in dendritic glutamate sensitivity (n = 7 neurons). The arrow indicates electrical 5 Hz stimulation (see A). The dashed line represents the 100% value.