Developmental Changes in Postnatal Murine Intestinal Interstitial Cell of Cajal Network Structure and Function

Abstract

The mammalian gastrointestinal (GI) tract undergoes rapid development during early postnatal life in order to transition from a milk to solid diet. Interstitial cells of Cajal (ICC) are the pacemaker cells that coordinate smooth muscle contractility within the GI tract, and hence we hypothesized that ICC networks undergo significant developmental changes during this early postnatal period. Numerical metrics for quantifying ICC network structural properties were applied on confocal ICC network imaging data obtained from the murine small intestine at various postnatal ages spanning birth to weaning. These imaging data were also coupled to a biophysically-based computational model to simulate pacemaker activity in the networks, to quantify how changes in structure may alter function. The results showed a pruning-like mechanism which occurs during postnatal development, and the temporal course of this phenomenon was defined. There was an initial ICC process overgrowth to optimize network efficiency and increase functional output volume. This was followed by a selective retaining and strengthening of processes, while others were discarded to further elevate functional output volume. Subsequently, new ICC processes were formed and the network was adjusted to its adult morphology. These postnatal ICC network developmental events may be critical in facilitating mature digestive function.

Continuous wavelet analysis of postprandial EGGs suggests sustained gastric slow waves may be slow to develop in infants with colic

“…Hence, the interposition of quasi‐regular periods of quiescence will tend to augment the lowest range of frequencies and may reduce the number of frequency components identified in the middle range. The Recent suggestion by Gao et al . that ‘pruning’ of intestinal ICC networks during maturation of the infant stomach is related to optimization of network function, and hence motility, after beginning of an oral diet, fits in with this hypothesis if we consider that optimal connectivity will eliminate bradygastric intervals that arise from annihilation of colliding slow waves in a poorly coordinated system.…”

“…Hence, the interposition of quasi-regular periods of quiescence will tend to augment the lowest range of frequencies and may reduce the number of frequency components identified in the middle range. The Recent suggestion by Gao et al13 that 'pruning' of intestinal ICC networks during maturation of the infant stomach is related to optimization of network function, and hence motility, after beginning of an oral diet, fits in with this hypothesis if we consider that optimal connectivity will eliminate bradygastric intervals that arise from annihilation of colliding slow waves in a poorly coordinated system.The consistently low number of the component frequencies, the ongoing variation in these frequencies over time and the consistencies in the ranges of the lower two frequencies detected on CWT analysis of the EGG recordings are similar to those reported on CWT of canine EGGs 31. These characteristics point to a greater fidelity of CWT compared with STFT methods with non-stationary signals as has been shown in other studies24 and point to their usefulness in the identification of subtle changes in signal characteristic such as may occur with EGG in infant colic.…”

A Stochastic Algorithm for Generating Realistic Virtual Interstitial Cell of Cajal Networks

“…ICC pacemaker activity was simulated over the training and virtual ICC networks using a biophysically-based computational model [22]. The ICC networks were discretized into a finite element triangular mesh, with each node point corresponding to a pixel in the ICC network imaging data.…”

“…Four measures were then used to quantitatively assess the simulated ICC pacemaker activity [22]: Activation rate : measures the rate at which the network achieves an average V m of −30 mV;Peak [Ca 2+ ] i ; Time to peak [Ca 2+ ] i ; Half peak [Ca 2+ ] i time ratio : gauges the dynamics of the [Ca 2+ ] i upstroke. …”

“…For the non-normalized measures of activation rate, peak [Ca 2+ ] i , and time to peak [Ca 2+ ] i , the relative errors of the measure values were computed, whereas for the normalized measure half peak [Ca 2+ ] i time ratio, the errors were computed relative to the range of the measure [22]. …”