Cellular automaton model for simulating tissue-specific intestinal electrophysiological activity

Abstract

Depletion of interstitial cell of Cajal (ICC) networks is known to occur in various gastrointestinal (GI) motility disorders. Although techniques for quantifying the structure of ICC networks are available, the ICC network structure-function relationships are yet to be well elucidated. Existing methods of relating ICC structure to function are computationally expensive, and it is difficult to up-scale them to larger multiscale simulations. A new cellular automaton model for simulating tissue-specific slow wave propagation was developed, and in preliminary studies the automaton model was applied on jejunal ICC network structures from wild-type and 5-HT2B receptor knockout (ICC depleted) mice. Two metrics were also developed to quantify the simulated propagation patterns: 1) ICC and 2) non-ICC activation lag metrics. These metrics measured the average delay in time taken for the slow wave to propagate across the ICC and non-ICC domain throughout the entire network compared to the theoretical fastest propagation, respectively. Slow wave propagation was successfully simulated across the ICC networks with greatly reduced computational time compared to previous methods, and the propagation pattern metrics quantitatively revealed an impaired propagation during ICC depletion. In conclusion, the developed slow wave propagation model and propagation pattern metrics offer a computationally efficient framework for relating ICC structure to function. These tools can now be further applied to define ICC structure-function relationships across various spatial and temporal scales.

Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens

“…Succolarity can be used as a measure of geometric connectivity of the ICC network in a particular direction, and therefore indicates the propensity of SWs to actively propagate in that direction via the ICC structure to generate a particular motility pattern The directions of Succolarity analyzed with respect to the wholemount confocal antral tissue are-serosal to mucosa (s2m), mucosa to serosal (m2s), anterior to posterior (a2p), posterior to anterior (p2a), proximal to distal (aboral), distal to proximal (oral) from resultant myoelectrical contractions. This present study emphasizes the significance of ICC structural connectivity on slow wave propagation, supported by compelling evidence from previous research [8,10]. The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum; suggesting that the intensity of longitudinal muscle contractions decreases aborally towards the terminal antrum possibly to restrict digesta from accelerating pass the pyloric region [26].…”

Spatial Noise in Coupling Strength and Natural Frequency within a Pacemaker Network; Consequences for Development of Intestinal Motor Patterns According to a Weakly Coupled Phase Oscillator Model

“…Arrays of cellular automata have been used to model slow wave propagation in the small intestine (Lammers et al, 2011 ; Gao et al, 2013b ). Lammers et al ( 2011 ) found that when an increasing percentage of cells were made inactive, propagation first slowed and then began to fail.…”

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

“…The ICC types constitute an intricate network, fundamental to GI electrophysiological activity (22). Importantly, cross-talk with the CNS exists and the ICC stimulate the sensory nerve of the GI tract through direct synaptic contact (38–40). The ICC are key to gastroenterological function and, conversely, the SCF/c-Kit axis is important for the development and phenotypic differentiation of the ICC, as well as ICC membrane polarization and pacemaker activity.…”