Figure 10.

Comparison between variable effects of NaF/NaP or Kv3 density reductions in the model and matching partial block experiments using TTX or 4-AP in brain slices. A, Examples of firing rate changes in whole-cell recordings after application of 10 and 15 nM TTX (left) and in the model when the two sodium conductances (NaF and NaP) were reduced twofold or fourfold with the same remaining conductance background (right). B, D, Examples of spike shape changes after TTX or 4-AP application (left panels) or reduction of NaF/NaP or KV3 conductances in the model (right panels). For the 4-AP and Kv3 manipulation, increases in spike amplitude (amp.) were seen in some recordings and in some models with specific combinations of other conductances present. Note that the spike width increased in all cases, but to a different degree. TTX application matched Na⁺ conductance manipulation in the model as smaller spike amplitudes resulted only in some recordings and for some model conductance backgrounds. C, Statistics of measure changes obtained after applying TTX in slice recordings (left column; n = 7 neurons; 7–10 nM TTX). The effects of multiple measures for all seven neurons recorded with one or two concentrations of TTX are given in supplemental Figure 4 (available at www.jneurosci.org as supplemental material). The range of observed effects of TTX on key measures generally matched the effect of a joint lowering of NaF and NaP conductance in model backgrounds (n = 10,206 models). In these box plots, red lines denote the population median, and the blue box denotes upper and lower quartiles. TTX, Experiment TTX. E, Two of eight recorded neurons exhibited doublets during 100 pA current injection after application of 4-AP, as did 4 of 11 model backgrounds randomly picked out of 1155 conductance backgrounds when their Kv3 conductance was lowered from 50 S/m². This feature was searched for manually because a measure of doublets was not present in our DB. In the example shown, the second spike in each doublet was more attenuated in amplitude in the experiment than the model. An additional reduction from 250 to 125 S/m² of the NaF conductance in the model also led to pronounced amplitude attenuation of second spikes in doublets (data not shown). Parameter backgrounds of the example models are listed in supplemental Table 7 (available at www.jneurosci.org as supplemental material).