An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combination of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular diffusion potentials and glial buffering currents. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for action potentials and dendritic calcium spikes in neurons, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. The edNEG model accounts for the concentration-dependent effects on ECS potentials that the standard models neglect. Using the edNEG model, we analyze these effects by splitting the extracellular potential into three components: one due to neural sink/source configurations, one due to glial sink/source configurations, and one due to extracellular diffusive currents. Through a series of simulations, we analyze the roles played by the various components and how they interact in generating the total slow potential. We conclude that the three components are of comparable magnitude and that the stimulus conditions determine which of the components that dominate. Author summary A common experimental method for investigating brain activity is to measure the electric potential outside neurons. These recordings usually only capture the high-frequency part of the potential while ignoring frequencies below a set cut-off between 0.1 and 1 Hz. Therefore, standard recordings cannot tell us what the slow frequency potentials might say about on-going brain activity. Most computational models are also not suited in this regard. They ignore two possibly important contributions to the slow potentials, namely the diffusion of ions in the extracellular space and a cell type called astrocytes that contribute to keeping an appropriate chemical environment for neurons. To overcome this, we here present what we call the electrodiffusive neuron-extracellular-glia model (edNEG) model for exploring the genesis of slow potentials in the brain. We use the model to study the contributions from neurons, astrocytes, and diffusive currents to the slow potentials and show that the model predicts that they are on the same order of magnitude.

Automated summary

The traditional computational models in computational neuroscience often neglect the simulation of glia cells and the extracellular space. The edNEG model presented in this study is the first to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics. This model offers a more comprehensive and realistic simulation of ion concentration dynamics in brain tissue.