Development of colonic motility in the neonatal mouse-studies using spatiotemporal maps

Abstract

Colonic migrating motor complexes (CMMCs) are spontaneous, anally propagating constrictions, repeating every 3-5 min in mouse colon in vitro. They are regulated by the enteric nervous system and may be equivalent to mass movement contractions. We examined postnatal development of CMMCs and circular muscle innervation to gain insight into mechanisms regulating transit in the maturing colon. Video recordings of mouse colon in vitro were used to construct spatiotemporal maps of spontaneous contractile patterns. Development of nitric oxide synthase (NOS) and cholinergic nerve terminals in the circular muscle was examined immunohistochemically. In adults, CMMCs appeared regularly at 4.6 +/- 0.9-min intervals (n = 5). These intervals were reduced by inhibition of NOS (2.7 +/- 0.2 min; n = 5; P < 0.05). CMMCs were abolished by tetrodotoxin (n = 4). CMMCs at postnatal day (P)10 were indistinguishable from adult. At birth and P4, CMMCs were absent. Instead, small constrictions that propagated both orally and anally, "ripples," were seen. Ripples were unaffected by tetrodotoxin or inhibition of NOS and were present in Ret(-/-) mice (which lack enteric neurons) at embryonic day 18.5. In P6 mice, only ripples were seen in control, but NOS inhibition induced CMMCs (n = 8). NOS terminals were abundant in the circular muscle at birth; cholinergic terminals were sparse but were common by P10. In mouse, myogenic ripples are the only mechanism available to produce colonic transit at birth. At P6, neural circuits that generate CMMCs are present but are inhibited by tonic activity of nitric oxide. Adult patterns appear by P10.

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

“…For instance, while some muscle contractions may change luminal diameter slightly and be visible on some STmaps (i.e., myogenic ripples) they may not actually cause any propulsion or mixing of intestinal contents 25 . This cannot be known without coupling of this technique to other functional measurements.…”

Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

“…Recently, Barnes and colleagues proposed that colonic tissue requires stimulation in order to observe CMMCs 32 , however published findings from our lab demonstrate that spontaneous CMMCs can be observed by simply pinning the tissue to the organ bath via the mesentery 7 . The presence of CMMCs under these conditions not only demonstrates the spontaneity of CMMCs, but further elaborates on the usefulness of this technique to establish changes in colonic motility.…”

“…Colonic migrating motor complexes (CMMCs) are spontaneous, neurogenic events that are the predominant motor pattern observed in isolated mouse colon in the absence of fecal pellets [4][5][6][7][8][9] . CMMCs are defined as rhythmic contractions that propagate along a horizontal distance that is at least half the total length of the colon (i.e., from the cecum to the rectum) 10 .…”

“…The effect of 5-HT inhibition on motility remains controversial, as conflicting data has been reported on the importance of endogenous 5-HT on colonic peristalsis and CMMCs 14,15 . Alterations in motility pre-and postnatally during development 7 , and the effects of gene mutations on gastrointestinal motility in animal models of disease 10 can also be examined by utilizing video imaging. Here we illustrate use of the method for a study of colonic motility in the NL3 R451C mouse model of autism, which expresses a missense mutation in the Nlgn3 gene encoding the synaptic adhesion protein Neuroligin-3 16 .…”

Le système nerveux entérique et l’unité neuro-glio-épithéliale digestive

“…Ainsi, il a été montré que la période post-natale est associée à une plasticité du phénotype neurochimique, caractérisée par une augmentation de la proportion de neurones cholinergiques responsables du développement de la motricité colique chez ces animaux (Roberts et al 2007 ;de Vries et al 2010). L'évolution du SNE au cours du jeune âge et de l'adolescence reste en revanche encore mal connue.…”