Frequency Preference Response to Oscillatory Inputs in Two-dimensional Neural Models: A Geometric Approach to Subthreshold Amplitude and Phase Resonance

Abstract

We investigate the dynamic mechanisms of generation of subthreshold and phase resonance in two-dimensional linear and linearized biophysical (conductance-based) models, and we extend our analysis to account for the effect of simple, but not necessarily weak, types of nonlinearities. Subthreshold resonance refers to the ability of neurons to exhibit a peak in their voltage amplitude response to oscillatory input currents at a preferred non-zero (resonant) frequency. Phase-resonance refers to the ability of neurons to exhibit a zero-phase (or zero-phase-shift) response to oscillatory input currents at a non-zero (phase-resonant) frequency. We adapt the classical phase-plane analysis approach to account for the dynamic effects of oscillatory inputs and develop a tool, the envelope-plane diagrams, that captures the role that conductances and time scales play in amplifying the voltage response at the resonant frequency band as compared to smaller and larger frequencies. We use envelope-plane diagrams in our analysis. We explain why the resonance phenomena do not necessarily arise from the presence of imaginary eigenvalues at rest, but rather they emerge from the interplay of the intrinsic and input time scales. We further explain why an increase in the time-scale separation causes an amplification of the voltage response in addition to shifting the resonant and phase-resonant frequencies. This is of fundamental importance for neural models since neurons typically exhibit a strong separation of time scales. We extend this approach to explain the effects of nonlinearities on both resonance and phase-resonance. We demonstrate that nonlinearities in the voltage equation cause amplifications of the voltage response and shifts in the resonant and phase-resonant frequencies that are not predicted by the corresponding linearized model. The differences between the nonlinear response and the linear prediction increase with increasing levels of the time scale separation between the voltage and the gating variable, and they almost disappear when both equations evolve at comparable rates. In contrast, voltage responses are almost insensitive to nonlinearities located in the gating variable equation. The method we develop provides a framework for the investigation of the preferred frequency responses in three-dimensional and nonlinear neuronal models as well as simple models of coupled neurons.