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.