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

Abstract

Pacemaker activities generated by networks of interstitial cells of Cajal (ICC), in conjunction with the enteric nervous system, orchestrate most motor patterns in the gastrointestinal tract. It was our objective to understand the role of network features of ICC associated with the myenteric plexus (ICC-MP) in the shaping of motor patterns of the small intestine. To that end, a model of weakly coupled oscillators (oscillators influence each other's phase but not amplitude) was created with most parameters derived from experimental data. The ICC network is a uniform two dimensional network coupled by gap junctions. All ICC generate pacemaker (slow wave) activity with a frequency gradient in mice from 50/min at the proximal end of the intestine to 40/min at the distal end. Key features of motor patterns, directly related to the underlying pacemaker activity, are frequency steps and dislocations. These were accurately mimicked by reduction of coupling strength at a point in the chain of oscillators. When coupling strength was expressed as a product of gap junction density and conductance, and gap junction density was varied randomly along the chain (i.e., spatial noise) with a long-tailed distribution, plateau steps occurred at pointsof low density. As gap junction conductance was decreased, the number of plateaus increased, mimicking the effect of the gap junction inhibitor carbenoxolone. When spatial noise was added to the natural interval gradient, as gap junction conductance decreased, the number of plateaus increased as before but in addition the phase waves frequently changed direction of apparent propagation, again mimicking the effect of carbenoxolone. In summary, key features of the motor patterns that are governed by pacemaker activity may be a direct consequence of biological noise, specifically spatial noise in gap junction coupling and pacemaker frequency.

Intra‐operative high‐resolution mapping of slow wave propagation in the human jejunum: Feasibility and initial results

“…We consider the disordered slow wave patterns observed in this study to likely be a normal physiological response to the intra‐operative experimental conditions, although these may not be reflective of normal in vivo , fed‐state physiology. The multiple dynamic pacemakers observed in this study could be reflective of normal intestinal function where a dynamic network of multiple pacemakers is known to play an important functional role, for example in segmentation . However, the degree and complexity of the disordered propagation could also be abnormal initiation and conduction, possibly due to intestinal handling or anesthesia, particularly because intestinal slow waves have been previously shown to entrain over much longer plateau distances .…”

The phase response and state space of slow wave contractions in the small intestine

“…Values of both ϕ and τ were normalized to T , the undisturbed contraction interval measured as the average of several full cycles before the pulse. Contraction waves always travelled distally, owing to the ICC natural frequency gradient (Parsons & Huizinga, , ). Therefore as each contraction wave approached the pulse time, ϕ decreased while d increased, generating a diagonal line of sample points across the (ϕ, d ) plane (Fig.…”

Noradrenaline inhibits neurogenic propulsive motor patterns but not neurogenic segmenting haustral progression in the rabbit colon

“…The propagating haustral boundary contractions have a very strong, stable rhythmicity at 0.5 cpm and can both be antegrade and be retrograde propagating. When an antegrade and a retrograde wave collide, both are annihilated, a feature that suggests a network of coupled oscillators underlying them . Several studies have concluded that the rhythmic propagation of the haustral boundaries is likely facilitated by ICC‐generated slow waves, an example of a neurally activated slow wave, hence a stimulus‐dependent slow wave .…”