A detailed biophysical model for a neuron/astrocyte network is developed in order to explore mechanisms responsible for the initiation and propagation of recurrent cortical spreading depolarizations. The model incorporates biophysical processes not considered in the earlier models. This includes a model for the Na-glutamate transporter, which allows for a detailed description of reverse glutamate uptake. In particular, we consider the specific roles of elevated extracellular glutamate and K in the initiation, propagation and recurrence of spreading depolarizations.

Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well-represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma. We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON's 1D mechanisms for ion channels, synapses, pumps, and so forth. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.

Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma. We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON's 1D mechanisms for ion channels, synapses, etc. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.