Mechanisms of generation of membrane potential resonance in a neuron with multiple resonant ionic currents.

David M Fox,Farzan Nadim,Horacio G Rotstein,Hua-An Tseng,Tomasz G Smolinski,Koen Vervaeke

doi:10.1371/journal.pcbi.1005565

Abstract

Neuronal 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.

Highlights

Neuronal network oscillations at characteristic frequency bands emerge from the coordinated activity of the participating neurons
Many neuron types exhibit membrane potential resonance (MPR) in which the neuron produces the largest response to oscillatory input at some preferred frequency and, in many systems, the network frequency is correlated with neuronal MPR
MPR has been observed in many neuron types such as those in the hippocampus [2,3,4] and entorhinal cortex [2,3,4,5,6], inferior olive [7, 8], thalamus [1, 9], striatum [10, 11], as well as in invertebrate oscillatory networks such as the pyloric network of the crustacean stomatogastric ganglion (STG) [12,13,14]

Summary

Introduction

Neuronal network oscillations at characteristic frequency bands emerge from the coordinated activity of the participating neurons. The slow resonant currents (or currents having resonant gating variables) oppose voltage changes and act as high-pass filters They include the hyperpolarization-activated inward current (IH) and the slow outward potassium current (IM). Most previous systematic mechanistic studies have primarily examined models with one resonant and one amplifying current, such as IH and INaP, respectively [15, 18,19,20] Currents having both activating and inactivating gating variables (in a multiplicative way) such as the low-threshold calcium current (ICa) are not included in this classification, but they are able to produce resonance by mechanisms that are less understood [16, 21]

Methods

Results

Discussion

Conclusion