A calibration - free electrode compensation method 1

12 In a single-electrode current clamp recording, the measured potential includes both the 13 response of the membrane and that of the measuring electrode. The electrode response is 14 traditionally removed using bridge balance, where the response of an ideal resistor representing 15 the electrode is subtracted from the measurement. Because the electrode is not an ideal resistor, 16 this procedure produces capacitive transients in response to fast or discontinuous currents. 17 More sophisticated methods exist, but they all require a preliminary calibration phase, to 18 estimate the properties of the electrode. If these properties change after calibration, the 19 measurements are corrupted. We propose a compensation method that does not require 20 preliminary calibration. Measurements are compensated offline, by fitting a model of the neuron 21 and electrode to the trace and subtracting the predicted electrode response. The error criterion 22 is designed to avoid the distortion of compensated traces by spikes. The technique allows 23 electrode properties to be tracked over time, and can be extended to arbitrary models of 24 electrode and neuron. We demonstrate the method using biophysical models and whole cell 25 recordings in cortical and brainstem neurons. 26