Computational modeling in neuroscience has largely focused on simulating the electrical activity of neurons, while ignoring other components of brain tissue, such as glial cells and the extracellular space. As such, most existing models can not be used to address pathological conditions, such as spreading depression, which involves dramatic changes in ion concentrations, large extracellular potential gradients, and glial buffering processes. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine multicompartmental 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 neuronal somatic action potentials, and dendritic calcium spikes, (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. We demonstrate that the edNEG model performs realistically as a local and closed system, i.e., that it maintains a steady state for moderate neural activity, but experiences concentration-dependent effects, such as altered firing patterns and homeostatic breakdown, when the activity level becomes too intense. Furthermore, we study the role of glia in making the neuron more tolerable to hyperactive firing and in limiting neuronal swelling. Finally, we discuss how the edNEG model can be integrated with previous spatial continuum models of spreading depression to account for effects of neuronal morphology, action potential generation, and dendritic Ca 2+ spikes which are currently not included in these models.
bioRxiv Subject Collection: Neuroscience