Frequency-domain analysis of membrane polarization in two-compartment model neurons with weak alternating electric fields.

Transcranial alternating current stimulation (tACS) is widely used in studying brain functions and the treatment of neuropsychiatric diseases in a frequency-specific manner. However, how tACS works on neuronal activity has been poorly understood. In this paper, we use linear system analysis to investigate how weak alternating electric fields (EFs) affect the membrane polarization of neurons in the frequency domain. Two biophysically realistic conductance-based two-compartment models of cortical pyramidal neurons are developed to simulate subthreshold membrane polarization with weak alternating EFs. We linearize the original nonlinear models at the stable equilibrium points and further simplify them to the two- or three-dimensional linear systems. Thus, we calculate the transfer functions of the low-dimensional linear models to model neuronal polarization patterns. Based on the transfer functions, we compute the amplitude- and phase-frequency characteristics to describe the relationship between weak EFs and membrane polarization. We also computed the parameters (gain, zeros, and poles) and structures (the number of zeros and poles) of transfer functions to reveal how neuronal intrinsic properties affect the parameters and structure of transfer functions and thus the frequency-dependent membrane polarization with alternating EFs. We find that the amplitude and phase of membrane polarization both strongly depended on EF frequency, and these frequency responses are modulated by the intrinsic properties of neurons. The compartment geometry, internal coupling conductance, and ionic currents (except