Large multiscale neuronal network simulations are of increasing value as more big data are gathered about brain wiring and organization under the auspices of a current major research initiative, such as Brain Research through Advancing Innovative Neurotechnologies. The development of these models requires new simulation technologies. We describe here the current use of the NEURON simulator with message passing interface (MPI) for simulation in the domain of moderately large networks on commonly available high-performance computers (HPCs). We discuss the basic layout of such simulations, including the methods of simulation setup, the run-time spike-passing paradigm, and postsimulation data storage and data management approaches. Using the Neuroscience Gateway, a portal for computational neuroscience that provides access to large HPCs, we benchmark simulations of neuronal networks of different sizes (500–100,000 cells), and using different numbers of nodes (1–256). We compare three types of networks, composed of either Izhikevich integrate-and-fire neurons (I&F), single-compartment Hodgkin-Huxley (HH) cells, or a hybrid network with half of each. Results show simulation run time increased approximately linearly with network size and decreased almost linearly with the number of nodes. Networks with I&F neurons were faster than HH networks, although differences were small since all tested cells were point neurons with a single compartment.

Calcium ( ) waves provide a complement to neuronal electrical signaling, forming a key part of a neuron’s second messenger system. We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate ( ), diffusible , receptors ( s), endoplasmic reticulum (ER) leak, and ER pump (SERCA) on ER. is released from ER stores via s upon binding of and . This results in -induced- -release (CICR) and increases spread. At least two modes of wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell and a pseudo-saltatory model where regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized distribution: (1) continuous homogeneous ER, (2) hotspots with increased density ( hotspots), and (3) areas of increased ER density (ER stacks). All three modes produced waves with velocities similar to those measured in vitro (approximately 50–90 m /sec). Continuous ER showed high sensitivity to density increases, with time to onset reduced and speed increased. Increases in SERCA density resulted in opposite effects. The measures were sensitive to changes in density and spacing of hotspots and stacks. Increasing the apparent diffusion coefficient of substantially increased wave speed. An extended electrochemical model, including voltage-gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent wave amplitude and duration. Our modeling suggests that pharmacological targeting of s and SERCA could allow modulation of wave propagation in diseases where dysregulation has been implicated.