Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis

Abstract

Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarized enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4 mm vs. 1.6 ± 1.2 mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.

Spatiotemporal Mapping of Motility in <em>Ex Vivo</em> Preparations of the Intestines

“…Video recording and spatiotemporal mapping of intestinal and colonic segments have been applied to a variety of species including zebrafish 26 , mouse 25,[27][28][29][30] , rat 7,9,[30][31][32][33] , guinea pig 5,6,8,[13][14][15][16][17][18][19]24,30,32,34,35 , brushtail possum 12,36 , rabbit 2,30,37,38 , chicken 39 , pig 40,41 and human 42 . The most widely studied species is the guinea pig.…”

“…The construction of STmaps and analysis of changes in motility pattern have been applied to key questions in the gastrointestinal motility of intestine and colon. These include: differentiation of neurogenic and myogenic contractions and defining the role of interstitial cells of Cajal 6,9,11,12,16,24,26,27,[29][30][31]33,[37][38][39][40]42 , understanding the complex interactions between the circular and longitudinal muscle layers 2,7,8,11,12,32,39,40 , examining the effects of intraluminal nutrients 10,18,19 , microbial strains 34 , and viscosities 12,36 on various motility patterns, and understanding the role of various endogenous neurohormonal agents and exogenous pharmacological agents 2,[4][5][6][7]9,10,[13][14][15][16][17]28,35,40 in the generation and modification of motility...…”

Interpreting manometric signals for propulsion in the gut

“…For this, we only considered the state of activation of the circular muscle. Peristaltic travelling waves were simulated on the basis of coordinated activation of polarised enteric neural pathways consisting of a ring of circular muscle contraction advancing in the aboral direction which is preceded by a region of active relaxation [3]. We simulated the effect of this propagating event on the signals of individual manometric sensors spaced along the lumen which represent the manometric probe.…”

“…Few models to date have attempted to adequately treat fluid-structure interactions between flexible wall and viscous fluid. Furthermore, such models also need to be able to include the dynamic local tightening and relaxing of the wall during peristalsis due to changing muscle states [3,4]. Detailed computational models of oesophageal motility [7] have helped to define relationships between motility and flow.…”

“…It took almost 100 years to describe the cellular nature of these enteric neural pathways [2]. Costa et al [3,4] have developed a method for indirect characterization of circular muscle state during peristalsis in animal models. This method is based on simultaneous manometric measurement and visualization of spatiotemporal variations in wall diameter.…”