Ephaptic coupling of cortical neurons

Abstract

The electrochemical processes that underlie neural function manifest themselves in ceaseless spatiotemporal field fluctuations. However, extracellular fields feed back onto the electric potential across the neuronal membrane via ephaptic coupling, independent of synapses. The extent to which such ephaptic coupling alters the functioning of neurons under physiological conditions remains unclear. To address this question, we stimulated and recorded from rat cortical pyramidal neurons in slices with a 12-electrode setup. We found that extracellular fields induced ephaptically mediated changes in the somatic membrane potential that were less than 0.5 mV under subthreshold conditions. Despite their small size, these fields could strongly entrain action potentials, particularly for slow (<8 Hz) fluctuations of the extracellular field. Finally, we simultaneously measured from up to four patched neurons located proximally to each other. Our findings indicate that endogenous brain activity can causally affect neural function through field effects under physiological conditions.

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Figure 1: Simultaneous recordings from up to 12 electrodes inside and outside a single neuron in rat slice during intra- and extracellular stimulation.
Figure 2: Subthreshold extracellular field entrainment.
Figure 3: Weak electric fields entrain spiking activity of individual neurons.
Figure 4: Ephaptic coupling leads to coordinated spiking activity among nearby neurons.

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Acknowledgements

We thank G. Buzsáki, U. Rutishauser and E. Schomburg for comments and discussions and J. Bastiaansen for assistance. This work was funded by the Engineering Physical Sciences Research Council (C.A.A.), the Sloan-Swartz Foundation (C.A.A.), the Swiss National Science Foundation (C.A.A.), EU Synapse (R.P.), the National Science Foundation (C.K. and C.A.A.), the Mathers Foundation (C.K. and C.A.A.) and the World Class University program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R31-10008, C.K.).

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C.A.A. and C.K. designed the experiments. C.A.A. and R.P. performed the experiments. C.A.A. wrote the codes and analyzed the data. C.A.A., R.P., H.M. and C.K. wrote the manuscript.

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Correspondence to Costas A Anastassiou.

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The authors declare no competing financial interests.

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Anastassiou, C., Perin, R., Markram, H. et al. Ephaptic coupling of cortical neurons. Nat Neurosci 14, 217–223 (2011). https://doi.org/10.1038/nn.2727

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