The motility of the gastrointestinal tract consists of local, non-propulsiv
e mixing (pendular or segmental) and propulsive (peristaltic) movements. It
is generally considered that mixing movements are produced by intrinsic pa
cemakers which generate rhythmic contractions, and peristalsis by intrinsic
excitatory and inhibitory neural reflex pathways, but the relationship bet
ween mixing and peristalsis is poorly understood. Peristalsis is compromise
d in mice lacking interstitial cells of Cajal, suggesting that these pacema
ker cells may also be involved in neural reflexes. Here we show that mixing
movements within longitudinal muscle result from spontaneously generated w
aves of elevated internal calcium concentration which originate from discre
te locations (pacing sites), spread with anisotropic conduction velocities
in all directions, and terminate by colliding with each other or with adjac
ent neurally suppressed regions. Excitatory neural reflexes control the spr
ead of excitability by inducing new pacing sites and enhancing the overall
frequency of pacing, whereas inhibitory reflexes suppress the ability of ca
lcium waves to propagate. We provide evidence that the enteric nervous syst
em organizes mixing movements to generate peristalsis, linking the neural r
egulation of pacemakers to both types of gut motility.