4.6 Article

Control of intrinsic pacemaker frequency and velocity of colonic migrating motor complexes in mouse

期刊

FRONTIERS IN NEUROSCIENCE
卷 8, 期 -, 页码 -

出版社

FRONTIERS RESEARCH FOUNDATION
DOI: 10.3389/fnins.2014.00096

关键词

colon; enteric nervous system; peristalsis; migrating motor complex; myenteric plexus

资金

  1. NH&MRC of Australia [APP1067317]

向作者/读者索取更多资源

The mechanisms that control the frequency and propagation velocity of colonic migrating motor complexes (CMMCs) in mammals are poorly understood. Previous in vitro studies on whole mouse colon have shown that CMMCs occur frequently (similar to every 1-3 min) when the colon is devoid of all fecal content. Consequently, these studies have concluded that the generation of CMMCs and the frequency which they occur does not require the presence of fecal content in the lumen. However, in these studies, stimuli have always been unavoidably applied to these empty colonic preparations, facilitating recordings of CMMC activity. We tested whether CMMCs still occur in empty whole colonic preparations, but when conventional recording methods are not used. To test this, we used video imaging, but did not utilize standard recording methods. In whole isolated colons containing multiple endogenous fecal pellets, CMMCs occurred frequently (1.9 +/- 0.1/min) and propagated at 2.2 +/- 0.2 mm/s. Surprisingly, when these preparations had expelled all content, CMMCs were absent in 11/24 preparations. In the remaining preparations, CMMCs occurred rarely (0.18 +/- 0.02/min) and at reduced velocities (0.71 +/- 0.1 mm/s), with reduced extent of propagation. When conventional recording techniques were then applied to these empty preparations, CMMC frequency significantly increased, as did the extent of propagation and velocity. We show that in contrast to popular belief, CMMCs either do not occur when the colon is free of luminal contents, or, they occur at significantly lower frequencies. We believe that previous in vitro studies on empty segments of whole mouse colon have consistently demonstrated CMMCs at high frequencies because conventional recording techniques stimulate the colon. This study shows that CMMCs are normally absent, or infrequent in an empty colon, but their frequency increases substantially when fecal content is present, or, if in vitro techniques are used that stimulate the intestine.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Neurosciences

Quantification of CGRP-immunoreactive myenteric neurons in mouse colon

Timothy J. Hibberd, Wai Ping Yew, Kelsi N. Dodds, Zili Xie, Lee Travis, Simon J. Brookes, Marcello Costa, Hongzhen Hu, Nick J. Spencer

Summary: This study comprehensively quantified CGRP+ myenteric neurons in mouse colon, which aligns with the expected range of an intrinsic primary afferent neuron (IPAN) marker.

JOURNAL OF COMPARATIVE NEUROLOGY (2022)

Article Gastroenterology & Hepatology

The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon

Paul T. Heitmann, Lauren Keightley, Lukasz Wiklendt, David A. Wattchow, Simon S. J. Brookes, Nicholas J. Spencer, Marcello Costa, Phil G. Dinning

Summary: This study aimed to describe the effects of loperamide on neuromuscular function in the human colon. The findings suggest that loperamide primarily alters colonic function by acting on inhibitory motor neurons or alternative non-opioid receptor pathways.

NEUROGASTROENTEROLOGY AND MOTILITY (2022)

Article Neurosciences

Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn

Kelsi N. Dodds, Melinda A. Kyloh, Lee Travis, Mack Cox, Tim J. Hibberd, Nick J. Spencer

Summary: This study investigated the distribution of thoracolumbar and lumbosacral spinal afferent neurons in the mouse uterine horn. The results showed that lumbosacral spinal afferent nerves provide relatively modest sensory innervation across the mouse uterine horn, with no regional specificity, compared to thoracolumbar spinal afferents.

FRONTIERS IN NEUROSCIENCE (2022)

Article Biology

Disengaging spinal afferent nerve communication with the brain in live mice

Melinda A. Kyloh, Timothy J. Hibberd, Joel Castro, Andrea M. Harrington, Lee Travis, Kelsi N. Dodds, Lukasz Wiklendt, Stuart M. Brierley, Vladimir P. Zagorodnyuk, Nick J. Spencer

Summary: This study developed a surgical method to selectively remove specific dorsal root ganglia (DRG) in mice, providing insights into the contribution of thoracolumbar and lumbosacral DRG to pain signaling and behavior. The technique allowed researchers to investigate sensory pathway functions in conscious, free-moving animals without genetic modification.

COMMUNICATIONS BIOLOGY (2022)

Article Neurosciences

Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity

Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu

Summary: By ablating the sensory channels TRPV1 and Piezo2 from colon-innervating neurons, the visceromotor responses (VMR) induced by colorectal distention (CRD) are significantly reduced in mice. Selective ablation of Piezo2 channels in TRPV1 lineage neurons reduces mechanically evoked visceral afferent action potential firing and CRD-induced VMR under physiological conditions, as well as in mouse models of zymosan-induced IBS and partial colon obstruction (PCO). These findings demonstrate the important role of the mechanosensitive Piezo2 channels in TRPV1-lineage neurons in visceral mechanosensitivity and nociception under physiological conditions, as well as in visceral hypersensitivity under pathological conditions.

NEURON (2023)

Article Neurosciences

How should we define a nociceptor in the gut-brain axis?

Nick J. Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu

Summary: In recent years, there has been increasing interest in understanding the communication between the gut and the brain. New data suggests that the sensory nerve pathways between the two may have a more significant impact on health and disease than previously assumed. While sensory nerve endings in the skin have been extensively studied, there is a lack of knowledge about most types of visceral afferents, especially those that innervate abdominal organs like the gut. Recent studies have identified nerve endings of spinal afferents in visceral organs, emphasizing their role in pain perception from the gut to the brain. Surprisingly, the majority of these spinal afferent nerve endings in the gut express the TRPV1 ion channel, commonly associated with nociceptive neurons. Furthermore, these nerve endings are activated at low thresholds within the normal physiological range, suggesting a complex nature of visceral nociception. This highlights the need to redefine nociceptors in the gut, which may involve multiple morphological types of spinal afferent nerve endings.

FRONTIERS IN NEUROSCIENCE (2022)

Article Physiology

Stimulation of extrinsic sympathetic nerves differentially affects neurogenic motor activity in guinea pig distal colon

David J. J. Smolilo, Timothy J. J. Hibberd, Marcello Costa, Phil G. G. Dinning, Lauren J. J. Keightley, Dayan De Fontgalland, David A. Wattchow, Nick J. J. Spencer

Summary: The speed of pellet propulsion in the isolated guinea pig distal colon in vitro is higher than in vivo measurements, suggesting inhibitory mechanisms from outside the gut. The study aimed to investigate the effects of sympathetic nerve stimulation on different motor behaviors of the distal colon. Results showed that electrical stimulation of colonic nerves inhibited transient neural events (TNEs) and pellet propulsion, while significant inhibition of colonic motor complexes (CMCs) required higher frequencies of stimulation. The findings suggest differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon and raise the possibility of paradoxical effects of CMCs on pellet movement suppression in vivo.

PHYSIOLOGICAL REPORTS (2023)

Article Pharmacology & Pharmacy

Endocannabinoids, anandamide and 2-AG, regulate mechanosensitivity of mucosal afferents in the Guinea pig bladder

Stewart Ramsay, Nick J. Spencer, Vladimir Zagorodnyuk

Summary: The aim of this study is to determine the role of endocannabinoids, anandamide (AEA) and 2-arachidonolylglycerol (2-AG), in regulating mechanosensitivity of probable nociceptive neurons innervating the bladder - capsaicin-sensitive mucosal afferents. The results showed that AEA potentiated the mechanical response of mucosal afferents, while 2-AG inhibited their response. These findings have important implications for understanding the role of endocannabinoids in regulating bladder sensation and function.

EUROPEAN JOURNAL OF PHARMACOLOGY (2023)

Article Immunology

Slowed gastrointestinal transit is associated with an altered caecal microbiota in an aged rat model

Nabil Parkar, Julie E. Dalziel, Nick J. Spencer, Patrick Janssen, Warren C. McNabb, Wayne Young

Summary: Gastrointestinal (GI) motility relies on the enteric nervous system (ENS) and is crucial for digestion. Dysfunction in the ENS can lead to constipation. Animal models have been developed to mimic constipation symptoms through pharmacological manipulations, and studies have shown an association between altered GI motility and gut microbial population. However, little is known about the changes in gut microbiota resulting from slowed GI motility induced by medication, and the current understanding is based on studies using faecal samples which do not accurately represent the intestinal microbiome. This study aimed to investigate how delayed GI transit, caused by opioid receptor agonism in the ENS, affects caecal microbiota composition, and the results showed significant differences in microbial composition between treatment groups, with Bacteroides being relatively abundant in the group with slowed GI transit.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2023)

Article Gastroenterology & Hepatology

Types of Neurons in the Human Colonic Myenteric Plexus Identified by Multilayer Immunohistochemical Coding

Bao Nan Chen, Adam Humenick, Wai Ping Yew, Lukasz Wiklendt, Phil G. Dinning, Nick J. Spencer, David A. Wattchow, Marcello Costa, Simon J. H. Brookes

Summary: This study used multiplexed immunohistochemistry to classify myenteric neurons of human colon into 20 classes. Cell morphology, soma size, and associations with axon terminals were quantified, providing a comprehensive understanding of the human myenteric plexus.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2023)

Review Physiology

Circadian rhythms in colonic function

Timothy J. Hibberd, Stewart Ramsay, Phaedra Spencer-Merris, Phil G. Dinning, Vladimir P. Zagorodnyuk, Nick J. Spencer

Summary: This review discusses the role of peripheral clocks in regulating major colonic functions, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. It also describes the interactions between pathophysiological states such as irritable bowel syndrome and ulcerative colitis and circadian rhythmicity.

FRONTIERS IN PHYSIOLOGY (2023)

Review Surgery

From the organ bath to the whole person: a review of human colonic motility

David A. Wattchow, Simon J. Brookes, Nick J. Spencer, Paul T. Heitmann, Roberto De Giorgio, Marcello Costa, Phil. G. Dinning

Summary: Motor function of the colon is crucial for health, and our understanding of its mechanisms is based on various experimental techniques. This article synthesizes key findings from these approaches to help surgeons better manage colonic conditions.

ANZ JOURNAL OF SURGERY (2023)

Proceedings Paper Gastroenterology & Hepatology

Rhythmicity in the Enteric Nervous System of Mice

Nick J. Spencer, Marcello Costa

Summary: The enteric nervous system (ENS) plays a crucial role in the cyclical motor activity of the gastrointestinal tract, but the activation of the thousands of neurons within the ENS that generate neurogenic contractions has remained a mystery. Neuronal imaging studies on the mouse large intestine have provided insights into how different classes of myenteric neurons are activated during cyclical motor patterns, and it has been found that large populations of myenteric neurons coordinate their firing across interconnected ganglia, regardless of their functional class. The polarity of the enteric circuits and the rhythmic activity of specific classes of enteric neurons at approximately 2 Hz are important factors in the propulsion of content along the mouse colon. The mechanisms that initiate and terminate the patterned firing of enteric neurons during cyclic activity remain to be determined, presenting an exciting challenge for future studies.

ENTERIC NERVOUS SYSTEM II (2022)

Proceedings Paper Gastroenterology & Hepatology

Activation of ENS Circuits in Mouse Colon: Coordination in the Mouse Colonic Motor Complex as a Robust, Distributed Control System

Bradley B. Barth, Nick J. Spencer, Warren M. Grill

Summary: The motor patterns of the colon are coordinated by the enteric nervous system (ENS) and involve various cell types. Recent advances in research have revealed the complexity of the circuitry underlying colonic motor patterns. The colonic motor complex (CMC) is described as a robust control system, and electrical stimulation can disrupt its coordination and propagation.

ENTERIC NERVOUS SYSTEM II (2022)

Proceedings Paper Gastroenterology & Hepatology

Identifying Types of Neurons in the Human Colonic Enteric Nervous System

Simon Brookes, Nan Chen, Adam Humenick, Marcello Costa, Phil Dinning, Paul Heitmann, Dominic Parker, David Smolilo, Nick J. Spencer, David Wattchow

Summary: Distinguishing and characterizing different classes of neurons in the enteric nervous system is a long-term goal for neuroscientists. While studies on enteric neurons in laboratory animals have been extensive, research on the human enteric nervous system is less advanced. Recent studies using single cell sequencing have made progress in classifying enteric neurons in mice and humans, but a comprehensive classification is yet to be achieved. This study presents preliminary data on a method to distinguish classes of myenteric neurons in the human colon using immunohistochemical, morphological, projection, and size data on single cells.

ENTERIC NERVOUS SYSTEM II (2022)

暂无数据