Limitations of Equivalent Circuit Models in Data-Driven Simulation of the Neuron-Electrode Interface

Abstract

Noninvasive neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and biosensors. Traditionally, neuron-electrode interfaces have been modeled as linear point or area contact equivalent circuits but such models have not been able to explain the shapes and magnitudes of the experimentally recorded extracellular signals. Also, previous work with Volterra-Wiener characterization of the planar neuron-microelectrode junction using bandlimited Gaussian white noise had shown that the mechanism of signal transduction across the nanoscale neuron-microelectrode cleft region might be nonlinear. In this optimization based study we compared and contrasted experimental and simulation data for point contact models of the extracellular ‘on-cell’ neuron-patch electrode and the planar neuron-microelectrode interface. The nonlinear contributions of the neurons to the dynamics of the equivalent circuit representation of the interfacial medium were systematically isolated by an independent estimation of the ion-channel parameters through a fitting of the simulated intracellular signals to the experimentally recorded voltage and current clamp signals. These ion-channel parameters were then employed in the optimization of the cell-electrode interface parameters based on extracellular recordings obtained from a neuron simultaneously interfaced to the ‘on-cell’ patch-electrode and the planar microelectrode using sub- and supra-threshold stimuli. An examination of the optimized model parameters for the experimental extracellular recordings from sub- and supra-threshold stimulations of the neuron-electrode junctions allowed us to draw important distinctions between the ‘on-cell’ neuron-patch electrode and neuron-microelectrode interfaces that could be attributed to the presence of electric double layer (EDL) and ionic electrodiffusion effects. Based on these results, we then discuss and point out the limitations of the equivalent circuit models in their failure to take account of the nonlinear EDL and ionic electrodiffusion effects occurring during the process of signal transduction at the neuron-electrode interface.