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Enteric nervous system electrophysiology

Nick J Spencer, Timothy J Hibberd, Lee Travis, Lukasz Wiklendt, Marcello Costa, Hongzhen Hu, Simon J Brookes, David A Wattchow, Phil G Dinning, Damien J Keating, Julian Sorensen
The enteric nervous system (ENS) contains millions of neurons essential for organization of motor behaviour of the intestine. It is well established the large intestine requires ENS activity to drive propulsive motor behaviours. However, the firing pattern of the ENS underlying propagating neurogenic contractions of the large intestine remains unknown. To identify this, we used high resolution neuronal imaging with electrophysiology from neighbouring smooth muscle. Myoelectric activity underlying propagating neurogenic contractions along murine large intestine (referred to as colonic migrating motor complexes, CMMCs) consisted of prolonged bursts of rhythmic depolarizations at a frequency of ∼2 Hz...
May 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Timothy J Hibberd, Jing Feng, Jialie Luo, Pu Yang, Vijay K Samineni, Robert W Gereau, Nigel Kelley, Hongzhen Hu, Nick J Spencer
BACKGROUND & AIMS: Strategies are needed to increase gastrointestinal transit without systemic pharmacologic agents. We investigated whether optogenetics, focal application of light to control enteric nervous system excitability, could be used to evoke propagating contractions and increase colonic transit in mice. METHODS: We generated transgenic mice with Cre-mediated expression of light-sensitive channelrhodopsin-2 (CHR2) in calretinin neurons (CAL-ChR2 Cre+ mice); Cre- littermates served as controls...
May 18, 2018: Gastroenterology
Michael A Grillo, Stephanie L Grillo, Bryan C Gerdes, Jacob G Kraus, Peter Koulen
Calsenilin is a calcium ion (Ca2+ )-binding protein involved in regulating the intracellular concentration of Ca2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca2+ signals entering the cytoplasm by releasing Ca2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry...
May 5, 2018: Molecular Neurobiology
Paola Brun, Hamid I Akbarali
In the enteric nervous system, neurons make contact with smooth muscle cells to regulate gastrointestinal functions. Since neuronal cell alterations and intestinal motor dysfunctions are strictly linked, in vitro models based on the culture of neurons or smooth muscle cells are of great advantage to elucidate the functions of the enteric nervous system under physiological and pathological conditions. In this chapter, we provide the protocol for isolation of neurons and smooth muscle cells from the myenteric plexus of adult mice...
2018: Methods in Molecular Biology
Phillip H Beske, Aaron B Bradford, Katie M Hoffman, Sydney J Mason, Patrick M McNutt
Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that block cholinergic release in the peripheral nervous system and cause death by asphyxiation. While post-exposure prophylaxis can effectively eliminate toxin in the bloodstream, there are no clinically effective treatments to prevent or reverse disease once BoNT has entered the neuron. To address the need for post-symptomatic countermeasures, we designed and developed an in vitro assay based on whole-cell, patch-clamp electrophysiological monitoring of miniature excitatory post-synaptic currents in synaptically active murine embryonic stem cell-derived neurons...
June 1, 2018: Toxicon: Official Journal of the International Society on Toxinology
Roman Chwedorowicz, Henryk Skarżyński, Weronika Pucek, Tadeusz Studziński
The results of contemporary studies confirm the formation of two neural networks in the brain during the period of adolescence. The first is defined as emotional, located in the limbic system, develops earlier, quicker, and more intensively than the second one in the prefrontal cortex, called the judgement network, which fulfils the role of control and inhibition of emotional reactions. The domination of the emotional network in adolescence is manifested by hyperactivity of the limbic system, accompanied by intensified undertaking of courageous, reckless, risky, or even sometimes dangerous actions, so very characteristic in the maturation...
March 22, 2017: Annals of Agricultural and Environmental Medicine: AAEM
Yiyuan Kang, Jia Liu, Bin Song, Xiaoli Feng, Lingling Ou, Limin Wei, Xuan Lai, Longquan Shao
Inorganic nanomaterials have been widely applied in biomedicine. However, several studies have noted that inorganic nanoparticles can enter the brain and induce cytoskeletal remodeling, as well as electrophysiological alterations, which are related to neurodevelopmental disorders and neurodegenerative diseases. The toxic effects of inorganic nanomaterials on the cytoskeleton and electrophysiology are summarized in this review. The relationships between inorganic NPs-induced cytoskeletal and electrophysiological alterations in the central nervous system remain obscure...
2016: Cellular Physiology and Biochemistry
W Li, L Huang, J Zeng, W Lin, K Li, J Sun, W Huang, J Chen, G Wang, Q Ke, J Duan, X Lai, R Chen, M Liu, Y Liu, T Wang, X Yang, Y Chen, H Xia, A P Xiang
The enteric nervous system (ENS) is recognized as a second brain because of its complexity and its largely autonomic control of bowel function. Recent progress in studying the interactions between the ENS and the central nervous system (CNS) has implicated alterations of the gut/brain axis as a possible mechanism in the pathophysiology of autism spectrum disorders (ASDs), Parkinson's disease (PD) and other human CNS disorders, whereas the underlying mechanisms are largely unknown because of the lack of good model systems...
March 2018: Molecular Psychiatry
Paul P Bertrand, Kate E Polglaze, Hui Chen, Shaun L Sandow, Anna Walduck, Trisha A Jenkins, Rebecca L Bertrand, Alan E Lomax, Lu Liu
Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors...
2016: Advances in Experimental Medicine and Biology
Jackie D Wood
Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus...
2016: Advances in Experimental Medicine and Biology
S E Carbone, V Jovanovska, S J H Brookes, K Nurgali
BACKGROUND: Patients receiving anticancer chemotherapy experience a multitude of gastrointestinal side-effects. However, the causes of these symptoms are uncertain and whether these therapeutics directly affect the enteric nervous system is unknown. Our aim was to determine whether the function and morphology of myenteric neurons are altered in specimens of the colon from chemotherapy-treated patients. METHODS: Colon specimens were compared from chemotherapy-treated and non-treated patients following colorectal resections for removal of carcinoma...
July 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Seung-Bum Ryoo, Heung-Kwon Oh, Sang Hui Moon, Eun Kyung Choe, Sung A Yu, Sung-Hye Park, Kyu Joo Park
Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity...
November 2015: Korean Journal of Physiology & Pharmacology
Johann K Mika, Karin Schwarz, Heinz D Wanzenboeck, Petra Scholze, Emmerich Bertagnolli
The regeneration of nerves of the peripheral nervous system after injuries is a complex process. This study presents a novel in vitro neurite regeneration concept to investigate the regeneration of neurons and their processes with different concentrations of neurotrophic factors. The core part of the concept is a transparent microfluidic neurite isolation (NI) device affixed on top of a microelectrode array (MEA), providing a fast and easy way to assess both the growth and the electrical activity of neurites...
November 2015: Journal of Neuroscience Research
Charles Kennedy
The role of adenosine 5'-triphosphate (ATP) as a major intracellular energy source is well-established. In addition, ATP and related nucleotides have widespread extracellular actions via the ionotropic P2X (ligand-gated cation channels) and metabotropic P2Y (G protein-coupled) receptors. Numerous experimental techniques, including myography, electrophysiology and biochemical measurement of neurotransmitter release, have been used to show that ATP has several major roles as a neurotransmitter in peripheral nerves...
September 2015: Autonomic Neuroscience: Basic & Clinical
K A McVey Neufeld, A Perez-Burgos, Y K Mao, J Bienenstock, W A Kunze
BACKGROUND: The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice...
May 2015: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
L V Filippova, A D Nozdrachev
On the basis of the electrophysiological research carried out with immunohystochemical methods on rats, it is found, that introduction of products of mast cell degranulation into blood as well as endogenous release of mast cell mediators with either the compound 48/80 or introduction of egg albumin to presensitized rats, enhances activity of mesenteric afferent nerve fibers. The obtained data provide evidence that intestinal afferents contribute an early signal to the brain regarding potential pathogens. The question of whether or not the intrinsic enteric neurons are involved in these processes, however, has not been carefully studied...
October 2014: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
Vivien Zell, Pierre-Éric Juif, Ulrike Hanesch, Pierrick Poisbeau, Fernand Anton, Pascal Darbon
Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3α5α-reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms...
February 2015: European Journal of Neuroscience
Stefan A Hoyng, Fred De Winter, Sara Gnavi, Ralph de Boer, Lennard I Boon, Laura M Korvers, Martijn R Tannemaat, Martijn J A Malessy, Joost Verhaagen
The clinical outcome of microsurgical repair of an injured peripheral nerve with an autograft is suboptimal. A key question addressed here is: can axon regeneration through an autograft be further improved? In this article the impact of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) on axon regeneration was compared after delivery to a 1cm long nerve autograft by gene therapy. To distinguish between early and late effects, regeneration was assessed at 2 and 20weeks post-surgery by histological, electrophysiological and functional analysis...
November 2014: Experimental Neurology
Jordan D Chambers, Joel C Bornstein, Rachel M Gwynne, Katerina Koussoulas, Evan A Thomas
Intrinsic sensory neurons (ISNs) of the enteric nervous system respond to stimuli such as muscle tension, muscle length, distortion of the mucosa, and the chemical content in the lumen. ISNs form recurrent networks that probably drive many intestinal motor patterns and reflexes. ISNs express a large number of voltage- and calcium-gated ion channels, some of which are modified by inflammation or repeated physiological stimuli, but how interactions between different ionic currents in ISNs produce both normal and pathological behaviors in the intestine remains unclear...
September 1, 2014: American Journal of Physiology. Gastrointestinal and Liver Physiology
R A Forsgård, R Korpela, L K Stenman, P Osterlund, R Holma
BACKGROUND: We have previously shown in mice that the fecal proportion and concentration of the hydrophobic bile acid deoxycholic acid (DCA) is elevated with high-fat feeding and that these changes are able to disrupt the intestinal barrier function. The aim of this study was to investigate whether these changes are mediated by the enteric nervous system (ENS). METHODS: The function of the ENS in the small intestinal tissues of mice was compromised by two different methods: by removing the seromuscular layer and by incubating the intact tissues with tetrodotoxin (TTX), a neural conduction blocker, before DCA treatment...
August 2014: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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