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Background: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherallyrestricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon. Methods: High-resolution video imaging was performed to monitor colonic wall diameter on isolated whole mouse colon. Regional changes in the effects of loperamide on the pattern generator underlying cyclical CMCs and their propagation across the full length of large intestine were determined. Results: The sensitivity of CMCs to loperamide across the length of colon varied significantly. Although there was a dose-dependent inhibition of CMCs with increasing concentrations of loperamide (10 nM - 1 mM), a major observation was that in the mid and distal colon, CMCs were abolished at low doses of loperamide (100 nM), while in the proximal colon, CMCs persisted at the same low concentration, albeit at a significantly slower frequency. Propagation velocity of CMCs was significantly reduced by 46%. The inhibitory effects of loperamide on CMCs were reversed by naloxone (1 mM). Naloxone alone did not change ongoing CMC characteristics. Discussion: The results show pronounced differences in the inhibitory action of loperamide across the length of large intestine. The most potent effect of loperamide to retard colonic transit occurred between the proximal colon and mid/distal regions of colon. One of the possibilities as to why this occurs is because the greatest density of mu opioid receptors are located on interneurons responsible for neuro-neuronal transmission underlying CMCs propagation between the proximal and mid/distal colon. The absence of effect of naloxone alone on CMC characteristics suggest that the mu opioid receptor has little ongoing constitutive activity under our recording conditions. [ABSTRACT FROM AUTHOR]

Gut motility undergoes a switch from myogenic to neurogenic control in late embryonic development. Here, we report on the electrical events that underlie this transition in the enteric nervous system, using the GCaMP6f reporter in neural crest cell derivatives. We found that spontaneous calcium activity is tetrodotoxin (TTX) resistant at stage E11.5, but not at E18.5. Motility at E18.5 was characterized by periodic, alternating high‐ and low‐frequency contractions of the circular smooth muscle; this frequency modulation was inhibited by TTX. Calcium imaging at the neurogenic‐motility stages E18.5–P3 showed that CaV1.2‐positive neurons exhibited spontaneous calcium activity, which was inhibited by nicardipine and 2‐aminoethoxydiphenyl borate (2‐APB). Our protocol locally prevented muscle tone relaxation, arguing for a direct effect of nicardipine on enteric neurons, rather than indirectly by its relaxing effect on muscle. We demonstrated that the ENS was mechanosensitive from early stages on (E14.5) and that this behaviour was TTX and 2‐APB resistant. We extended our results on L‐type channel‐dependent spontaneous activity and TTX‐resistant mechanosensitivity to the adult colon. Our results shed light on the critical transition from myogenic to neurogenic motility in the developing gut, as well as on the intriguing pathways mediating electro‐mechanical sensitivity in the enteric nervous system. Highlights: What is the central question of this study?What are the first neural electric events underlying the transition from myogenic to neurogenic motility in the developing gut, what channels do they depend on, and does the enteric nervous system already exhibit mechanosensitivity?What is the main finding and its importance?ENS calcium activity is sensitive to tetrodotoxin at stage E18.5 but not E11.5. Spontaneous electric activity at fetal and adult stages is crucially dependent on L‐type calcium channels and IP3R receptors, and the enteric nervous system exhibits a tetrodotoxin‐resistant mechanosensitive response. Abstract figure legend Tetrodotoxin‐resistant Ca2+ rise induced by mechanical stimulation in the E18.5 mouse duodenum. [ABSTRACT FROM AUTHOR]

Motor function of the colon is essential for health. Our current understanding of the mechanisms that underlie colonic motility are based upon a range of experimental techniques, including molecular biology, single cell studies, recordings from muscle strips, analysis of part or whole organ ex vivo through to in vivo human recordings. For the surgeon involved in the clinical management of colonic conditions this amounts to a formidable volume of material. Here, we synthesize the key findings from these various experimental approaches so that surgeons can be better armed to deal with the complexities of the colon. [ABSTRACT FROM AUTHOR]

Background and Aims: Viscerofugal neurons (VFNs) have cell bodies in the myenteric plexus and axons that project to sympathetic prevertebral ganglia. In animals they activate sympathetic motility reflexes and may modulate glucose metabolism and feeding. We used rapid retrograde tracing from colonic nerves to identify VFNs in human colon for the first time, using ex vivo preparations with multi-layer immunohistochemistry. Methods: Colonic nerves were identified in isolated preparations of human colon and set up for axonal tracing with biotinamide. After fixation, labeled VFN cell bodies were subjected to multiplexed immunohistochemistry for 12 established nerve cell body markers. Results: Biotinamide tracing filled 903 viscerofugal nerve cell bodies (n = 23), most of which (85%) had axons projecting orally before entering colonic nerves. Morphologically, 97% of VFNs were uni-axonal. Of 215 VFNs studied in detail, 89% expressed ChAT, 13% NOS, 13% calbindin, 9% enkephalin, 7% substance P and 0 of 123 VFNs expressed CART. Few VFNs contained calretinin, VIP, 5HT, CGRP, or NPY. VFNs were often surrounded by dense baskets of axonal varicosities, probably reflecting patterns of connectivity; VAChT+ (cholinergic), SP+ and ENK+ varicosities were most abundant around them. Human VFNs were diverse; showing 27 combinations of immunohistochemical markers, 4 morphological types and a wide range of cell body sizes. However, 69% showed chemical coding, axonal projections, soma-dendritic morphology and connectivity similar to enteric excitatory motor neurons. Conclusion: Viscerofugal neurons are present in human colon and show very diverse combinations of features. High proportions express ChAT, consistent with cholinergic synaptic outputs onto postganglionic sympathetic neurons in prevertebral ganglia. [ABSTRACT FROM AUTHOR]

Australian neuroscientists at the turn of the twentieth century and in the succeeding decades faced formidable obstacles to communication and supply due to their geographical isolation from centers of learning in Europe and North America. Consequently, they had to spend significant periods of their lives overseas for training and experience. The careers of six pioneers—Laura Forster, James Wilson, Grafton Elliot Smith, Alfred Campbell, Raymond Dart, and John Eccles—are presented in the form of vignettes that address their lives and most enduring scientific contributions. All six were medically trained and, although they never collaborated directly with one another, they were linked by their neuroanatomical interests and by shared mentors, who included Nobelists Ramon y Cajal and Charles Sherrington. By the 1960s, as the so-called "tyranny of distance" was overcome by advances in communication and transport technology, local collaborative groups of neuroscientists emerged in several Australian university departments that built on the individual achievements of these pioneers. This in turn led to the establishment of the Australasian Neuroscience Society in 1981. [ABSTRACT FROM AUTHOR]

This article discusses the propagation of slow waves in the stomach and the use of extracellular recordings to study this phenomenon. The authors conducted a study using high-resolution mapping and extracellular electrode arrays in anesthetized rats to investigate how slow waves propagate along the distal stomach. They found that slow waves propagate in an antegrade direction, with some regional variation, and that the amplitude and velocity of propagation vary in different regions of the stomach. The study also confirmed that extracellular recordings are a reliable technique for studying gastric slow waves. Overall, this research provides valuable insights into the coordination of gastric peristalsis and the characteristics of slow wave propagation in the stomach. [Extracted from the article]