Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue

PLoS Comput Biol. 2016 Nov 7;12(11):e1005193. doi: 10.1371/journal.pcbi.1005193. eCollection 2016 Nov.


Recorded potentials in the extracellular space (ECS) of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1) the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2) the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i) ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii) The power spectral density (PSD) of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii) Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in experimental recordings.

MeSH terms

  • Animals
  • Computer Simulation
  • Diffusion
  • Electromagnetic Fields
  • Extracellular Fluid / chemistry
  • Extracellular Fluid / physiology*
  • Humans
  • Ion Channel Gating / physiology
  • Ions / chemistry
  • Ions / metabolism*
  • Membrane Potentials / physiology*
  • Models, Chemical
  • Models, Neurological*
  • Nerve Net / chemistry
  • Nerve Net / physiology*
  • Neurons / chemistry
  • Neurons / physiology*


  • Ions

Grants and funding

This project was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 604102 (Human Brain Project, HBP), and the Research Council of Norway (NFR, through ISP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.