Extracellular detection of active membrane currents in the neuron-electrode interface

Although measurement of sealing resistance is an important tool in the assessment of the electrical contacts between cultured cells and substrate embedded microelectrodes, it does not offer information about the type of cell, i.e. neuron or non-neuronal cell. Also, rules for translation of a measured sealing resistance into parameters for successful stimulation, i.e. eliciting an action potential, are not available yet. Therefore, a method is proposed for the detection of active membrane currents, elicited by extracellular current stimulation. The method is based on the prediction of the linear part of the response to an applied stimulus current pulse using an impedance model of the neuron–electrode contact. Active membrane currents are detected in the nonlinear response, which is obtained by subtraction of the predicted linear response from the measured response. The required impedance model parameters are extracted from impedance spectroscopy or directly from the measured responses.