Mechanisms of generation of membrane potential resonance in a neuron with multiple resonant ionic currents
AbstractNeuronal membrane potential resonance (MPR) is associated with subthreshold and network oscillations. A number of voltage-gated ionic currents can contribute to the generation or amplification of MPR, but how the interaction of these currents with linear currents contributes to MPR is not well understood. We explored this in the pacemaker PD neurons of the crab pyloric network. The PD neuron MPR is sensitive to blockers of H- (IH) and calcium-currents (ICa). We used the impedance profile of the biological PD neuron, measured in voltage clamp, to constrain parameter values of a conductance-based model using a genetic algorithm and obtained many optimal parameter combinations. Unlike most cases of MPR, in these optimal models, the values of resonant- (fres) and phasonant- (fφ=0) frequencies were almost identical. Taking advantage of this fact, we linked the peak phase of ionic currents to their amplitude, in order to provide a mechanistic explanation the dependence of MPR on the ICa gating variable time constants. Additionally, we found that distinct pairwise correlations between ICa parameters contributed to the maintenance of fres and resonance power (QZ). Measurements of the PD neuron MPR at more hyperpolarized voltages resulted in a reduction of fres but no change in QZ. Constraining the optimal models using these data unmasked a positive correlation between the maximal conductances of IH and ICa. Thus, although IH is not necessary for MPR in this neuron type, it contributes indirectly by constraining the parameters of ICa.Author SummaryMany neuron types exhibit membrane potential resonance (MPR) in which the neuron produces the largest response to oscillatory input at some preferred (resonant) frequency and, in many systems, the network frequency is correlated with neuronal MPR. MPR is captured by a peak in the impedance vs. frequency curve (Z-profile), which is shaped by the dynamics of voltage-gated ionic currents. Although neuron types can express variable levels of ionic currents, they may have a stable resonant frequency. We used the PD neuron of the crab pyloric network to understand how MPR emerges from the interplay of the biophysical properties of multiple ionic currents, each capable of generating resonance. We show the contribution of an inactivating current at the resonant frequency in terms of interacting time constants. We measured the Z-profile of the PD neuron and explored possible combinations of model parameters that fit this experimentally measured profile. We found that the Z-profile constrains and defines correlations among parameters associated with ionic currents. Furthermore, the resonant frequency and amplitude are sensitive to different parameter sets and can be preserved by co-varying pairs of parameters along their correlation lines. Furthermore, although a resonant current may be present in a neuron, it may not directly contribute to MPR, but constrain the properties of other currents that generate MPR. Finally, constraining model parameters further to those that modify their MPR properties to changes in voltage range produces maximal conductance correlations.