In the guinea pig distal colon, nonpropulsive neurally mediated motor patterns have been observed in different experimental conditions. Isolated segments of guinea pig distal colon were used to investigate these neural mechanisms by simultaneously recording wall motion, intraluminal pressure, and smooth muscle electrical activity in different conditions of constant distension and in response to pharmacological agents. Three distinct neurally dependent motor patterns were identified: transient neural events (TNEs), cyclic motor complexes (CMC), and distal colon migrating motor complexes (DCMMC). These could occur simultaneously and were distinguished by their electrophysiological, mechanical, and pharmacological features. TNEs occurred at irregular intervals of ~3s, with bursts of action potentials at 9 Hz. They propagated orally at 12 cm/s via assemblies of ascending cholinergic interneurons that activated final excitatory and inhibitory motor neurons, apparently without involvement of stretch-sensitive intrinsic primary afferent neurons. CMCs occurred during maintained distension and consisted of clusters of closely spaced TNEs, which fused to cause high-frequency action potential firing at 7 Hz lasting ~10 s. They generated periodic pressure peaks mediated by stretch-sensitive intrinsic primary afferent neurons and by cholinergic interneurons. DCMMCs were generated by ongoing activity in excitatory motor neurons without apparent involvement of stretch-sensitive neurons, cholinergic interneurons, or inhibitory motor neurons. In conclusion, we have identified three distinct motor patterns that can occur concurrently in the isolated guinea pig distal colon. The mechanisms underlying the generation of these neural patterns likely involve recruitment of different populations of enteric neurons with distinct temporal activation properties.
CMCs are a distinctive neurally dependent cyclic motor pattern, that emerge with distension over long lengths of the distal colon. They do not require changes in muscle tension or contractility to entrain the neural activity underlying CMC propagation. CMCs are likely to play an important role interacting with the neuromechanical processes that time the propulsion of multiple natural pellets and may be particularly relevant in conditions of impaction or obstruction, where long segments of colon are simultaneously distended.
Key points Enteric neural circuits enable isolated preparations of guinea‐pig distal colon to propel solid and fluid contents by a self‐sustaining neuromechanical loop process. In addition there are at least three neural mechanisms which are not directly involved in propulsion: cyclic motor complexes, transient neural events and distal colon migrating motor complexes. In excised guinea‐pig colon we simultaneously recorded high resolution manometry, video‐imaging of colonic wall movements and electrophysiological recordings from smooth muscle, which enabled us to identify mechanisms that underlie the propulsion of colonic content. The results show that the intermittent propulsion during emptying of the multiple natural faecal pellets is due to the intermittent activation of cyclic motor complexes and this is facilitated by transient neural events. Loss or dysfunction of these activities is likely to underlie disordered gastrointestinal transit. Abstract It is well known that there are different patterns of electrical activity in smooth muscle cells along different regions of the gastrointestinal tract. These different patterns can be generated by myogenic and/or neurogenic mechanisms. However, what patterns of electrical activity underlie the propulsion of natural faecal content remains unknown, particularly along the large intestine, where large quantities of water are reabsorbed and semi‐solid faeces form. In this study, we developed a novel approach which enables for the first time the simultaneous recording of high resolution intraluminal manometry, electrophysiology from the smooth muscle, and spatio‐temporal video imaging of colonic wall movements. Using this approach we were able to reveal the nature of enteric neuromuscular transmission and patterns of motor activity responsible for the movement of content. Three distinct neurogenic patterns of electrical activity were recorded even in the absence of propulsive movement. These were the cyclic motor complexes (CMCs), the transient neural events (TNEs) and the slowly propagating distal colonic migrating motor complexes (DCMMCs). We present evidence that the initiation of pellet propulsion is due to a cyclic motor complex (CMC) occurring oral to the pellet. Furthermore, we discovered that the intermittent propulsion of natural faecal pellets is generated by intermittent activation of CMCs; and this propulsion is facilitated by hexamethonium‐sensitive TNEs. However, TNEs were not required for propulsion. The findings reveal the patterns of electrical activity that underlie propulsion of natural colonic content and demonstrate that propulsion is generated by a complex interplay between distinct enteric neural circuits.
Background: In herbivores, the proximal and distal colonic regions feature distinct motor patterns underlying formation and propulsion of fecal pellets, respectively.Omnivores, such as mice and humans, lack a similar clear anatomical transition between colonic regions. We investigated whether distinct processes form and propel content along the large intestine of a mouse (an omnivore). Methods: We recorded propulsive and non-propulsive neurogenic motor activity in mouse large intestine under six different stimulus conditions of varying viscosities. Gut wall movements were recorded by video and smooth muscle electrical behavior recorded with extracellular suction electrodes. Key Results: Three major neurally mediated motor patterns contributed to pellet formation and propulsion. (1) Pellet-shaped boluses are pinched off near the cecocolonic junction and slowly propelled distally to a transition located at 40% length along the colon. (2) At this functional colonic flexure, propulsion speed is significantly increased by self-sustaining neural peristalsis. Speed transition at this location also occurs with artificial pellets and with spontaneously formed boluses in the empty colon. (3) Periodic colonic motor complexes (CMCs) were present in all conditions reaching a maximal frequency of about 0.4 cpm and extending across the proximal and distal colon with faster speed of propagation. Conclusions and Inferences:The three motor patterns share a unique underlying fundamental property of the enteric circuits, which involve extended ensembles of enteric neurons firing at close to 2 Hz. The demonstration of distinct functional differences between proximal and distal colon in rabbit, guinea pig, and now mouse raises the possibility that this may be an organizational principle in other mammalian species, including humans.
Neurally dependent cyclic motor patterns, some of which do not directly cause propulsive movements, occur in the large intestine of many species. 1 They have been described in detail in isolated guinea pig colon 2-5 mouse colon 6-8 and isolated human colon. 9 In the mouse colon, one of the major colonic motor patterns has been described as colonic migrating motor complexes and studied extensively. [10][11][12][13][14][15][16][17] Since these events do not always propagate in one direction, they are now more generally referred to as colonic motor complexes CMCs. 18,19 CMCs depend on activity of the enteric nervous system. In mice, they are generated by coordinated and synchronized firing of large
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