Title: Homogenization of a Spatially Extended, Stochastic Ion Channel Model
Abstract: Simulations of stochastic neuron potential models, which describe the voltage potential along the length of a neuron's axon and incorporate ion channel noise as Gaussian fluctuations, have shown that channel noise can induce complex phenomena such as jitters and splitting of action potentials [1] and place constraints on the miniaturization of axons [2]. To develop a robust analytic framework for understanding stochastic effects of channel noise on action potential propagation in a neuron, we need to begin by investigating how many, independent and spatially distributed ion channels can collectively yield deterministic behavior. We start with an electrophysiological derivation of a simple discrete model and contrast this with a common, yet less physically accurate approach where the law of large numbers and the central limit theorem are more easily applied. Our model couples a spatially discretized diffusive PDE for the voltage with continuous-time Markov processes that govern the behavior of the ion channels. We will then outline an argument using homogenization theory to estimate the rate of strong convergence to the typical deterministic PDE as the spacing between ion channels approaches zero. Finally, we present a numerical technique for simulating our model and discuss the challenges involved in increasing computational efficiency of simulations.
[1] Faisal AA, Laughlin SB. Stochastic simulations on the reliability of action potential propagation in thin axons. PLoS Comput Biol. 2007 May;3(5):e79. doi: 10.1371/journal.pcbi.0030079. PMID: 17480115; PMCID: PMC1864994.
[2] Faisal AA, White JA, Laughlin SB. Ion-channel noise places limits on the miniaturization of the brain's wiring. Curr Biol. 2005 Jun 21;15(12):1143-9. doi: 10.1016/j.cub.2005.05.056. PMID: 15964281.