Increase in sodium conductance decreases firing rate and gain in model neurons.

We studied the effects of increased sodium conductance on firing rate and gain in two populations of conductance-based, single-compartment model neurons. The first population consisted of 1000 model neurons with differing values of seven voltage-dependent conductances. In many of these models, increasing the sodium conductance threefold unexpectedly reduced the firing rate and divisively scaled the gain at high input current. In the second population, consisting of 1000 simplified model neurons, we found that enhanced sodium conductance changed the frequency-current (FI) curve in two computationally distinct ways, depending on the firing rate. In these models, increased sodium conductance produced a subtractive shift in the FI curve at low firing rates because the additional sodium conductance allowed the neuron to respond more strongly to equivalent input current. In contrast, at high input current, the increase in sodium conductance resulted in a divisive change in the gain because the increased conductance produced a proportionally larger activation of the delayed rectifier potassium conductance. The control and sodium-enhanced FI curves intersect at a point that delimits two regions in which the same biophysical manipulation produces two fundamentally different changes to the model neuron's computational properties. This suggests a potentially difficult problem for homeostatic regulation of intrinsic excitability.