Parallel Stochastic Discrete Event Simulation of Calcium Dynamics in Neuron

IEEE/ACM Trans Comput Biol Bioinform. 2019 May-Jun;16(3):1007-1019. doi: 10.1109/TCBB.2017.2756930. Epub 2017 Sep 26.

Abstract

The intra-cellular calcium signaling pathways of a neuron depends on both biochemical reactions and diffusions. Some quasi-isolated compartments (e.g., spines) are so small and calcium concentrations are so low that one extra molecule diffusing in by chance can make a nontrivial difference in concentration (percentage-wise). These rare events can affect dynamics discretely in such a way that they cannot be evaluated by a deterministic and continuous simulation. Stochastic models of such a system provide a more detailed understanding of these systems than existing deterministic models because they capture their behavior at a molecular level. Our research focuses on the development of a high performance parallel discrete event simulation environment, Neuron Time Warp (NTW), which is intended for use in the parallel simulation of stochastic reaction-diffusion systems such as intra-calcium signaling. NTW is integrated with NEURON, a simulator which is widely used within the neuroscience community. We simulate two models, a calcium buffer and a calcium wave model. The calcium buffer model is employed in order to verify the correctness and performance of NTW by comparing it to a sequential deterministic simulation in NEURON. We also derived a discrete event calcium wave model from a deterministic model using the stochastic $\text{IP}_{3}\text{R}$IP3R structure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Calcium / metabolism*
  • Calcium Signaling*
  • Computational Biology
  • Computer Simulation
  • Cytosol / metabolism
  • Diffusion
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / chemistry
  • Models, Neurological
  • Neurons / metabolism*
  • Probability
  • Programming Languages
  • Software
  • Stochastic Processes

Substances

  • Inositol 1,4,5-Trisphosphate Receptors
  • Calcium