The controlled progression of contents along the gastrointestinal tract is an essential part of digestion. Different patterns of intestinal movements are involved in the physiological progression of contents along the digestive tract and are the result of the interplay between spontaneous activity of intestinal smooth muscle and enteric neural circuits (Costa & Furness, 1982;Huizinga et al. 1998). Almost one hundred years ago, Bayliss and Starling (1899) revealed the presence of polarized reflex pathways in the intestine and suggested that they were responsible for the propulsion of contents. The analysis of intestinal propulsion was significantly advanced by Trendelenburg in 1917 who showed that reproducible propulsive motor patterns could be triggered in isolated segments of guinea-pig ileum by liquid distension. This form of intestinal peristalsis elicited in vitro is dependent on the activation of enteric circuits as many investigators have demonstrated (Kosterlitz, 1968;Tonini et al. 1981;Waterman et al. 1994b).Slow distension of isolated segments of guinea-pig intestine by liquid infusion produces a neurally-mediated shortening of the longitudinal muscle (Kosterlitz & Robinson, 1959) and an increase in diameter coinciding with an inhibitory reflex mechanism involving nitric oxide (intestinal accommodation; Waterman et al. 1994a). This initial response to liquid distension has been named the 'preparatory phase' (Trendelenburg, 1917;Kosterlitz, 1968). At a threshold volume or intraluminal pressure, a contraction of the circular muscle occurs at the oral end and propagates aborally to empty the segment. This propulsive event is called the 'emptying phase' and involves the activation of different enteric neural pathways (Waterman & Costa, 1994;Waterman et al. 1994b). Despite the common description of this motor behaviour as the 'peristaltic reflex' (Kosterlitz, 1968), it has become apparent that there is a sequential activation of neural

Segments of isolated guinea‐pig intestine, 12 mm long, were distended slowly by intraluminal fluid infusion or by mechanical stretch as either a tube or flat sheet. In all cases, at a constant threshold length, a sudden, large amplitude contraction of the circular muscle occurred orally, corresponding to the initiation of peristalsis. Circumferential stretch of flat sheet preparations evoked graded contractions of the longitudinal muscle (the ‘preparatory phase’), which were maintained during circular muscle contraction. This suggests that the lengthening reported during the emptying phase of peristalsis is due to mechanical interactions. The threshold for peristalsis was lower with more rapid stretches and was also lower in long preparations (25 mm) compared with short preparations (5‐10 mm), indicating that ascending excitatory pathways play a significant role in triggering peristalsis. Stretching a preparation beyond the threshold for peristalsis evoked contractions of increasing amplitude; thus peristalsis is graded above its threshold. However, during suprathreshold stretch maintained at a constant length, contractions of the circular muscle quickly declined in amplitude and frequency. Circular muscle cells had a resting membrane potential approximately 6 mV more negative than the threshold for action potentials. During slow circumferential stretch, subthreshold graded excitatory motor input to the circular muscle occurred, prior to the initiation of peristalsis. However, peristalsis was initiated by a discrete large excitatory junction potential (12 ± 2 mV) which evoked bursts of smooth muscle action potentials and which probably arose from synchronized firing of ascending excitatory neuronal pathways.

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Background Parkinson's disease is a progressive neurodegenerative disorder that results in the widespread loss of select classes of neurons throughout the nervous system. The pathological hallmarks of Parkinson's disease are Lewy bodies and neurites, of which α‐synuclein fibrils are the major component. α‐Synuclein aggregation has been reported in the gut of Parkinson's disease patients, even up to a decade before motor symptoms, and similar observations have been made in animal models of disease. However, unlike the central nervous system, the nature of α‐synuclein species that form these aggregates and the classes of neurons affected in the gut are unclear. We have previously reported selective expression of α‐synuclein in cholinergic neurons in the gut (J Comp Neurol. 2013; 521:657), suggesting they may be particularly vulnerable to degeneration in Parkinson's disease. Methods In this study, we used immunohistochemistry to detect α‐synuclein oligomers and fibrils via conformation‐specific antibodies after rotenone treatment or prolonged exposure to high [K+] in ex vivo segments of guinea‐pig ileum maintained in organotypic culture. Key Results Rotenone and prolonged raising of [K+] caused accumulation of α‐synuclein fibrils in the axons of cholinergic enteric neurons. This took place in a time‐ and, in the case of rotenone, concentration‐dependent manner. Rotenone also caused selective necrosis, indicated by increased cellular autofluorescence, of cholinergic enteric neurons, labeled by ChAT‐immunoreactivity, also in a concentration‐dependent manner. Conclusions & Inferences To our knowledge, this is the first report of rotenone causing selective loss of a neurochemical class in the enteric nervous system. Cholinergic enteric neurons may be particularly susceptible to Lewy pathology and degeneration in Parkinson's disease.

Enteric viscerofugal neurons provide a pathway by which the enteric nervous system (ENS), otherwise confined to the gut wall, can activate sympathetic neurons in prevertebral ganglia. Firing transmitted through these pathways is currently considered fundamentally mechanosensory. The mouse colon generates a cyclical pattern of neurogenic contractile activity, called the colonic motor complex (CMC). Motor complexes involve a highly coordinated firing pattern in myenteric neurons with a frequency of ;2 Hz. However, it remains unknown how viscerofugal neurons are activated and communicate with the sympathetic nervous system during this naturally-occurring motor pattern. Here, viscerofugal neurons were recorded extracellularly from rectal nerve trunks in isolated tube and flat-sheet preparations of mouse colon held at fixed circumferential length. In freshly dissected preparations, motor complexes were associated with bursts of viscerofugal firing at 2 Hz that aligned with 2-Hz smooth muscle voltage oscillations. This behavior persisted during muscle paralysis with nicardipine. Identical recordings were made after a 4-to 5-d organotypic culture during which extrinsic nerves degenerated, confirming that recordings were from viscerofugal neurons. Single unit analysis revealed the burst firing pattern emerging from assemblies of viscerofugal neurons differed from individual neurons, which typically made partial contributions, highlighting the importance and extent of ENS-mediated synchronization. Finally, sympathetic neuron firing was recorded from the central nerve trunks emerging from the inferior mesenteric ganglion. Increased sympathetic neuron firing accompanied all motor complexes with a 2-Hz burst pattern similar to viscerofugal neurons. These data provide evidence for a novel mechanism of sympathetic reflex activation derived from synchronized firing output generated by the ENS.