Figure 6.
a, The simulated NMDA spike is not dependent on dendritic Na+ current. To examine whether the Na+ conductance in the basal dendrites of the simulated pyramidal cell (Rhodes and Gray, 1994; Rhodes et al., 1995; Antic, 2003) might be responsible for the initiation or generation of NMDA spikes, Na+ channels were turned off in the simulation, and synaptic input of 1 nS AMPA and 4 nS NMDA (∼33% above threshold here) was applied to each of two adjacent 23 μm subsegments at the location indicated on the inset, with 1 mm [Mg2+]. As in the corresponding TTX experiment in vitro (Schiller et al., 2000), dendritic Na+ current was not required for production of the NMDA spike. A comparison of the simulated response to that in control conditions indicates that the involvement of Na+ current is limited to the beginning of the NMDA spike and does not control its duration. The small boost at the beginning of the event was consistent with the finding (Schiller et al., 2000) that threshold NMDA conductance was slightly lowered by the presence of Na+ (observed in simulation; data not shown). It was concluded that, like AMPA, Na+ conductance boosts initiation but thereafter has a limited role in the generation of simulated NMDA events. Accordingly, at threshold levels of input (data not shown), application of TTX required an increase in synaptic NMDA conductance, as seen in vitro (Schiller et al., 2000). b, Dendritic Ca2+ conductance affects the duration and amplitude of NMDA spikes. High-threshold Ca2+ current exists in layer 5 intrinsically bursting pyramidal cell dendrites and is instrumental in driving the bursts in simulations of this cell type (Rhodes and Gray, 1994). To address whether dendritic Ca2+ current participated in either the initiation or generation of NMDA spikes, it was eliminated in the simulation, here done in 1 mm [Mg2+], and a suprathreshold input (applied at the location shown in the inset, with a synaptic conductance of 1 nS AMPA and 4 nS NMDA to each of two adjacent 23 μm compartments) was applied, in 1 mm [Mg2+]. The level of dendritic high-threshold Ca conductance was then systematically varied. Although the NMDA spike could be produced at any level of dendritic Ca2+ current, consistent with an experimental report in vitro (Schiller et al., 2000), in simulations Ca2+ current did contribute importantly to the amplitude and width of the NMDA spike events. Interestingly, at low levels of gCa density, the NMDA spike lengthened because of the reduced effect of Ca2+-gated K+ currents. It is concluded that Ca2+ contributes importantly to driving NMDA spikes and that Ca2+-gated K+ currents can also shape their duration. c, The NMDA spike is much more sensitive to NMDA conductance magnitude. The comparative sensitivity of NMDA spikes to NMDA conductance was examined by varying that parameter while both the dendritic Na+ and Ca2+ conductance levels were at the highest levels used in a and b. The NMDA spike was not produced below a minimum level of NMDA conductance, regardless of the presence of dendritic Na+ and Ca2+ sufficient to make the branch highly intrinsically excitable, illustrating the predominant role of NMDA current in these events, even within intrinsically excitable dendrites. d, NMDA spikes in more proximal branches show similarly limited involvement of dendritic Na+ channels. The role of Na+ current in the generation of the NMDA spike was examined in a proximal branch in the same manner as in a. Here a larger synaptic conductance was necessary because of the lower input impedance of the proximal branch, and the amplitude of the somatic EPSP was much greater. Despite these differences, here again the elimination of Na+ currents curtailed neither the amplitude nor the duration of the NMDA spike, further supporting the conclusion that although Na+ currents may reduce the threshold synaptic amplitude that is required (data not shown), they play a minor role in the generation of NMDA spikes.