Spiking resonances in models with the same slow resonant and fast amplifying currents but different subthreshold dynamic properties

Horacio G. Rotstein

The generation of spiking resonances in neurons (preferred spiking responses to oscillatory inputs) requires the interplay of the intrinsic ionic currents that operate at the subthreshold voltage level and the spiking mechanisms. Combinations of the same types of ionic currents in different parameter regimes may give rise to different types of nonlinearities in the voltage equation (e.g., parabolic- and cubic-like), generating subthreshold (membrane potential) oscillations patterns with different properties. These nonlinearities are not apparent in the model equations, but can be uncovered by plotting the voltage nullclines in the phase-plane diagram. We investigate the spiking resonant properties of conductance-based models that are biophysically equivalent at the subthreshold level (same ionic currents), but dynamically different (parabolic- and cubic-like voltage nullclines). As a case study we consider a model having a persistent sodium and a hyperpolarization-activated (h-) currents, which exhibits subthreshold resonance in the theta frequency band. We unfold the concept of spiking resonance into evoked and output spiking resonance. The former focuses on the input frequencies that are able to generate spikes, while the latter focuses on the output spiking frequencies regardless of the input frequency that generated these spikes. A cell can exhibit one or both types of resonances. We also measure spiking phasonance, which is an extension of subthreshold phasonance (zero-phase-shift response to oscillatory inputs) to the spiking regime. The subthreshold resonant properties of both types of models are communicated to the spiking regime for low enough input amplitudes as the voltage response for the subthreshold resonant frequency band raises above threshold. For higher input amplitudes evoked spiking resonance is no longer present in these models, but output spiking resonance is present primarily in the parabolic-like model due to a cycle skipping mechanism (involving mixed-mode oscillations), while the cubic-like model shows a better 1:1 entrainment. We use dynamical systems tools to explain the underlying mechanisms and the mechanistic differences between the resonance types. Our results demonstrate that the effective time scales that operate at the subthreshold regime to generate intrinsic subthreshold oscillations, mixed-mode oscillations and subthreshold resonance do not necessarily determine the existence of a preferred spiking response to oscillatory inputs in the same frequency band. The results discussed in this paper highlight both the complexity of the suprathreshold responses to oscillatory inputs in neurons having resonant and amplifying currents with different time scales and the fact that the identity of the participating ionic currents is not enough to predict the resulting patterns, but additional dynamic information, captured by the geometric properties of the phase-space diagram, is needed.