Sensitivity to Strain and Shear Stress of Isolated Mechanosensitive Enteric Neurons

Kugler, Eva Maria; Michel, Klaus; Kirchenbüchler, David; Dreissen, Georg; Csiszár, Ágnes; Merkel, Rudolf; Schemann, Michael; Mazzuoli‐Weber, Gemma

doi:10.1016/j.neuroscience.2017.12.052

Cited by 17 publications

(13 citation statements)

References 52 publications

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“…The SMP instead is located beneath the mucosa and is largely responsible for the regulation of epithelial functions including secretion and absorption (Furness, 2000;Gwynne & Bornstein, 2007). Neurons of the ENS can be activated by various stimuli, detecting mechanical deformation as well as intraluminal chemical stimuli (Bertrand et al 1997;Neunlist et al 1999;Schemann et al 2002;Mazzuoli & Schemann, 2009, 2012Mazzuoli-Weber & Schemann, 2015a;Kugler et al 2018). The simplified classification of enteric neurons into sensory neurons, motor neurons and interneurons has been revised over the last few years.…”

Section: Introductionmentioning

confidence: 99%

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Submucosal enteric neurons of the cavine distal colon are sensitive to hypoosmolar stimuli

Kollmann

Elfers

Maurer

et al. 2020

The Journal of Physiology

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Neurons of the enteric submucous plexus are challenged by osmolar fluctuations during digestion and absorption of nutrients. r Central neurons are very sensitive to changes in osmolality but knowledge on that issue related to enteric neurons is sparse. r The present study focuses on investigation of osmosensitivity of submucosal neurons including potential molecular mediating mechanisms. r Results show that submucosal neurons respond to hypoosmolar stimuli with increased activity which is partially mediated by the transient receptor potential vanilloid 4 channel. r We provided important information on osmosensitive properties of enteric neurons. These data are fundamental to better explain the nerve-mediated control of the gastrointestinal functions during physiological and pathophysiological (diarrhoea) conditions.

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Section: Introductionmentioning

confidence: 99%

“…2002; Mazzuoli & Schemann, 2009, 2012; Mazzuoli‐Weber & Schemann, 2015a; Kugler et al . 2018). The simplified classification of enteric neurons into sensory neurons, motor neurons and interneurons has been revised over the last few years.…”

Section: Introductionmentioning

confidence: 99%

Submucosal enteric neurons of the cavine distal colon are sensitive to hypoosmolar stimuli

Kollmann

Elfers

Maurer

et al. 2020

The Journal of Physiology

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“…We call v COM the displacement per unit time of the fluid's centre of mass, and ε the average stretch (strain) of the tube diameter (figure 1b). During the simulation, we measure ε since this is a controlling mechanism of peristalsis [19] that is going to play an important role in the next sections. During each contraction, the intestine can be divided into three regions (figure 1c).…”

Section: The Multiphysics Model Without An Artificial Neural Network (Non-adaptive Model)mentioning

confidence: 99%

The virtual physiological human gets nerves! How to account for the action of the nervous system in multiphysics simulations of human organs

Alexiadis

Simmons

Stamatopoulos

et al. 2021

J. R. Soc. Interface.

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This article shows how to couple multiphysics and artificial neural networks to design computer models of human organs that autonomously adapt their behaviour to environmental stimuli. The model simulates motility in the intestine and adjusts its contraction patterns to the physical properties of the luminal content. Multiphysics reproduces the solid mechanics of the intestinal membrane and the fluid mechanics of the luminal content; the artificial neural network replicates the activity of the enteric nervous system. Previous studies recommended training the network with reinforcement learning. Here, we show that reinforcement learning alone is not enough; the input–output structure of the network should also mimic the basic circuit of the enteric nervous system. Simulations are validated against in vivo measurements of high-amplitude propagating contractions in the human intestine. When the network has the same input–output structure of the nervous system, the model performs well even when faced with conditions outside its training range. The model is trained to optimize transport, but it also keeps stress in the membrane low, which is exactly what occurs in the real intestine. Moreover, the model responds to atypical variations of its functioning with ‘symptoms’ that reflect those arising in diseases. If the healthy intestine model is made artificially ill by adding digital inflammation, motility patterns are disrupted in a way consistent with inflammatory pathologies such as inflammatory bowel disease.

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“…Enteric neurons can be activated by various stimuli, including chemical stimuli as well as mechanical distortion 11 – 17 . During muscle contraction and relaxation enteric neurons are constantly exposed to distorting forces 16 , 18 .…”

Section: Introductionmentioning

confidence: 99%

“…With intracellular recording techniques it has been shown that MEN in the MP respond to distension as well as to mucosal distortion 20 – 22 . An important step forward was the use of imaging techniques, as they allowed to record simultaneously from a larger set of neurons and were also a prerequisite to study enteric neurons in larger animals 14 – 17 , 23 , 24 . Using von Frey hair probing and intraganglionic volume injection, compression sensitive MEN have been identified in the MP of the guinea pig gastric corpus, ileum and colon 14 , 16 , 23 as well as in mouse ileum and colon 15 .…”

Section: Introductionmentioning

confidence: 99%

Compression and stretch sensitive submucosal neurons of the porcine and human colon

Filzmayer

Elfers

Michel

et al. 2020

Sci Rep

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The pig is commonly believed to be a relevant model for human gut functions-however, there are only a few comparative studies and none on neural control mechanisms. To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. We used neuroimaging techniques to record responses to tensile or compressive forces in submucous neurons. Compression and stretch caused Ca-transients and immediate spike discharge in 5-11% of porcine and 15-24% of human enteric neurons. The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Most of the MEN expressed choline acetyltransferase and substance P; nitric oxide synthase-positive MEN primarily occurred in distal colon. The findings reveal common features of MEN in human and pig colon which we interpret as a result of species-independent evolutionary conservation rather than a specific functional proximity between the two species. The enteric nervous system (ENS), which is integrated into the wall of the gastrointestinal tract (GIT) from the oesophagus to the anal sphincter, enables the GIT to generate reflex activity independent from central influences 1-3. The ENS is organized in two complex neuronal networks called the submucosal plexus (SMP) and the myenteric plexus (MP). In both, the pig and human the SMP consists of two layers interconnected by interganglionic nerve fiber tracts 4,5. The SMP regulates mostly epithelial functions, such as secretion and absorption, as well as blood flow, cell proliferation and immune responses. The distinct parts of the SMP are called inner SMP (ISMP) and outer SMP (OSMP) with the ISMP being located closely to the lamina muscularis mucosae, whereas the OSMP is located on the luminal side of the circular muscle layer 6. In the porcine and human colon mainly neurons in the ISMP predominantly project to the mucosa 7-9 , and hence likely regulate epithelial functions 10. Enteric neurons can be activated by various stimuli, including chemical stimuli as well as mechanical distortion 11-17. During muscle contraction and relaxation enteric neurons are constantly exposed to distorting forces 16,18. Remarkably, even enteric neurons classically defined as interneurons or motoneurons are mechanosensitive, suggesting that mechanosensitive enteric neurons (MEN) are multifunctional 14,15,19. With intracellular recording techniques it has been shown that MEN in the MP respond to distension as well as to mucosal distortion 20-22. An important step forward was the use of imaging techniques, as they allowed to record simultaneously from a larger set of neurons and were also a prerequisite to study enteric neurons in larger animals 14-17,23,24. Using von Frey hair probing and intraganglionic volume injection, compression sensitive MEN have been identified in the MP of the guinea pig gastric corpus, ileum and colon 14,16,23 as well as in mouse ileum and colon 15. Furthermore, von Frey hair probing was used to identify compression sensitive MEN in isol...

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Sensitivity to Strain and Shear Stress of Isolated Mechanosensitive Enteric Neurons

Cited by 17 publications

References 52 publications

Submucosal enteric neurons of the cavine distal colon are sensitive to hypoosmolar stimuli

Submucosal enteric neurons of the cavine distal colon are sensitive to hypoosmolar stimuli

The virtual physiological human gets nerves! How to account for the action of the nervous system in multiphysics simulations of human organs

Compression and stretch sensitive submucosal neurons of the porcine and human colon

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