~ Pergamon Neuroscience Vol. 73, No. l, pp. 287-297, 1996 Copyright © 1996 IBRO. Published by ElsevierScienceLtd. All rights reserved Printed in Great Britain S0306-4522(96)00040-1 0306-4522/96 $15.00 + 0.00 DISSOCIATION OF THE ASCENDING REFLEX FROM PERISTALSIS IN THE SMALL INTESTINE EXCITATORY GUINEA-PIG M. TONINI,* M. COSTA, S. J. H. BROOKES and C. M. S. HUMPHREYS Department of Human Physiology and Centre for Neuroscience, School of Medicine, The Flinders University of South Australia, GPO Box 2100, Adelaide 5001, South Australia A~traet--Localized distension of the intestine evokes an ascending excitatory reflex and a descending inhibitory reflex in the circular muscle layer. The sequential activation of these two reflexes is believed to underlie the motor pattern of peristalsis, which is responsible for the co-ordinated propulsion of intestinal contents. In this study we have shown that the initiation of peristalsis involves mechanisms additional to those mediating the ascending excitatory reflex. A short length of guinea-pig small intestine was mounted in a partitioned organ bath so that the lumen was occluded by the partition, but neuronal continuity was maintained. The anal segment was distended by intraluminal fluid infusion to evoke a peristalsis; in the oral segment, an isotonic transducer was used to record circular muscle contractions due to ascending excitatory reflexes. Stepwise distension of the anal segment with 5 #1 increments at 10 s intervals, or with a large, single-step infusion, elicited both the ascending excitatory reflex and peristalsis, when carried out at 3 min intervals. The threshold volume for the ascending excitatory reflex was smaller than the threshold for peristalsis with either incremental or single-step distensions. The ascending excitatory reflex appeared with a shorter delay than peristalsis. Tetrodotoxin (0.6pM) or hexamethonium (100/~M) added to the oral compartment abolished the ascending excitatory reflex but not peristalsis. These drugs abolished both the ascending excitatory reflex and peristalsis when added to the anal compartment. When stimuli were delivered at 1 min intervals, peristalsis failed completely after the first trial, but the ascending excitatory reflex persisted, at a slightly reduced amplitude. When the anal segment was distended to just-subthreshold volume, electrical field stimulation (0.254).5 ms, 1-5 Hz for 1 s), delivered at 3 min intervals, evoked ascending excitatory responses but not peristalsis. Higher frequency stimulation (10 Hz) consistently evoked both peristalsis and the ascending excitatory responses. When trains of electrical stimulation were repeated at 1 min intervals, peristalsis quickly failed, but the ascending excitatory response persisted, although reduced in amplitude. The initiation of peristalsis can be dissociated from the ascending excitatory reflex by its threshold volume, by the duration of distension or the intensity of electrical stimulation required, and by its susceptibility to fatigue with repeated mechanical or electrical stimuli. This suggests that the ascending excitatory reflex may be part of the mechanism underlying the initiation of peristalsis, but that additional mechanisms must also be involved. Peristalsis should not be regarded as a reflex response but rather as an all-or-nothing motor pattern, triggered by mechanical stimulation, similar to other co-ordinated motor patterns in vertebrates and invertebrates. Copyright © 1996 IBRO. Published by Elsevier Science Ltd. Key words: motor pattern, enteric nervous system, myenteric plexus, motility, neuronal circuit, pattern generator. Localized distension of the wall of the intestine evokes a contraction oral to the point of stimulation (the ascending excitatory reflex) and a relaxation anally (the descending inhibitory reflex). These polar- ized reflexes are due to neuronal circuits within the wall of the intestine that form the basis of the "law of the intestine" described by Bayliss and Starling. The polarized ascending excitatory and descending inhibitory reflexes have been analysed in detail in isolated segments of intestine by recording either the mechanical 14"23'34 or the electrical 21'3° activity of the *To whom correspondence should be addressed. Abbreviations: AH, afterhyperpolarizing; TTX, tetrodo- toxin. circular muscle. These two polarized reflexes do not propagate and can be considered as standing reflexes. Intestinal peristalsis, in contrast, is a stereotyped motor pattern, involving co-ordinated sequential contraction and relaxation of the intestinal smooth muscle layers, that is responsible for the anal propul- sion of intraluminal contents. Like the polarized reflexes, peristalsis is mediated by neuronal circuits contained entirely within the intestine, ~5'24 so it too can be studied in isolated segments of small intestine s'24'35'37'4° or large intestine. 14'36 In an isolated segment of guinea-pig small intes- tine, peristalsis can be initiated in a reproducible manner by infusing fluid into the lumen. Peristalsis consists of a wave of circular muscle contraction 287