Seeing beyond the spikes: Reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings.

Even though electrophysiologists have been routinely recording intracellular neural activity ever since the groundbreaking work of Hodgkin and Huxley and extracellular multi-channel electrodes have also been frequently and extensively used, a practical experimental method to track membrane potential changes along a complete single neuron is still lacking. Instead of obtaining multiple intracellular measurements on the same neuron, we propose an alternative method by combining single-channel somatic patch-clamp and multi-channel extracellular potential recordings. In this work, we show that it is possible to reconstruct the complete spatiotemporal distribution of the membrane potential of a single neuron with the spatial resolution of an extracellular probe during action potential generation. Moreover, the reconstruction of the membrane potential allows for distinguishing between the two major but previously hidden components of the current source density (CSD) distribution: the resistive and the capacitive currents. This distinction provides a clue to the clear interpretation of the CSD analysis, as the resistive component corresponds to transmembrane ionic currents: all the synaptic, voltage-sensitive, and passive currents; while capacitive currents are considered the main contributors of counter-currents. We validate our model-based reconstruction approach on simulations and demonstrate its application to experimental data obtained in vitro via paired extracellular and intracellular recordings from a single pyramidal cell of the rat hippocampus. In perspective, the estimation of the spatial distribution of resistive membrane currents makes the distinction possible between active and passive sinks and sources of the CSD map and the localization of the synaptic input currents, which make the neuron fire. Abstract figure legend In this work, we show that it is possible to reconstruct the complete spatiotemporal distribution of the membrane potential of a single neuron, with the spatial resolution of an extracellular probe, by combining single-channel somatic patch-clamp and multi-channel extracellular potential recordings during action potential generation. The model-based membrane potential reconstruction utilizes the detailed morphology of the neuron and allows for distinguishing between the two major but previously hidden components of the current source density (CSD) distribution: the resistive and the capacitive currents. This distinction provides a clue to the clear interpretation of the CSD analysis, as the resistive component corresponds to transmembrane ionic currents: all the synaptic, voltage-sensitive, and passive currents; while capacitive currents are considered the main contributors of counter-currents. In perspective, the estimation of the spatial distribution of resistive membrane currents makes possible the localization of the synaptic input currents, which make the neuron fire. This article is protected by copyright. All rights reserved.