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Modern neurophysiological experiments frequently involve multiple channels separated by very small distances. A unique methodological concern for multiple-electrode experiments is that of capacitive coupling (cross-talk) between channels. Yet the nature of the cross-talk recording circuit is not well known in the field, and the extent to which it practically affects neurophysiology experiments has never been fully investigated. Here we describe a simple electrical circuit model of simultaneous recording and stimulation with two or more channels and experimentally verify the model using ex vivo brain slice and in vivo whole-brain preparations. In agreement with the model, we find that cross-talk amplitudes increase nearly linearly with the impedance of a recording electrode and are larger for higher frequencies. We demonstrate cross-talk contamination of action potential waveforms from intracellular to extracellular channels, which is observable in part because of the different orders of magnitude between the channels. This contamination is electrode impedance-dependent and matches predictions from the model. We use recently published parameters to simulate cross-talk in high-density multichannel extracellular recordings. Cross-talk effectively spatially smooths current source density (CSD) estimates in these recordings and induces artefactual phase shifts where underlying voltage gradients occur; however, these effects are modest. We show that the effects of cross-talk are unlikely to affect most conclusions inferred from neurophysiology experiments when both originating and receiving electrode record signals of similar magnitudes. We discuss other types of experiments and analyses that may be susceptible to cross-talk, techniques for detecting and experimentally reducing cross-talk, and implications for high-density probe design. NEW &amp; NOTEWORTHY We develop and experimentally verify an electrical circuit model describing cross-talk that necessarily occurs between two channels. Recorded cross-talk increased with electrode impedance and signal frequency. We recorded cross-talk contamination of spike waveforms from intracellular to extracellular channels. We simulated high-density multichannel extracellular recordings and demonstrate spatial smoothing and phase shifts that cross-talk enacts on CSD measurements. However, when channels record similar-magnitude signals, effects are modest and unlikely to affect most conclusions.

Magnitude and behavior of cross-talk effects in multichannel electrophysiology experiments