Neurogastroenterology Laboratory

Biotinamide filling in the gut

Micrograph shows extrinsic axons in mouse gut labelled with biotinamide – a technique developed in our laboratory to reveal extrinsic nerve branching patterns

The gastrointestinal tract is a tube, along which contents are pushed by the coordinated movements of its muscular wall. These movements are controlled mainly by the enteric nervous system, an extensive network of nerve cells that lies in the wall of the mammalian gastrointestinal tract. It is the largest division of the autonomic nervous system and contains approximately the same number of neurones as the spinal cord. The central nervous system receives information from the digestive tract via extrinsic sensory neurons, with cell bodies in nodose and dorsal root ganglia. These pathways give rise to sensation from the gut and also lead to activation of the sympathetic and parasympathetic pathways to the gut. Our laboratory studies many aspects of gut neuronal function and in recent years has extended these approaches to understanding the neural control of the bladder.

Much of our current research aims to understand the functioning of the sensory pathways which run from the gut to the central nervous system. We are interested in identifying the different types of extrinsic sensory neurons, the type of information they convey and how they are activated. These neurons play important roles in diverse reflexes and sensations, ranging from hunger and satiety, controlling gut motility, conveying sensations of rectal urgency and, of course, activating pain pathways. We study these neurons electrophysiologically, morphologically, immunohistochemically and increasingly are applying molecular biological techniques to understand the molecular basis of their function. Many of the techniques that we use have been developed or substantially optimised within the laboratory, to characterise visceral sensory neurons in detail.

Investigators

Simon JH Brookes, BSc(Hons), PhD, Professor & Head of Department of Human Physiology
Marcello Costa, MD, FAA, MS&D Professor of Neurophysiology
David A Wattchow, PhD, FRACS Consultant Surgeon
Vladimir Zagorodnyuk, PhD, Senior Research Officer, NHMRC Chief Investigator A

Visiting Research Fellows / Scholars

Dr James Brock, Prince of Wales Medical Research Institute
Dr Marc Gladman, The Royal London Hospital, UK

Support staff

Bao Nan Chen, BMed, MSc, Research Assistant
Alison Wadey, BSc(Hons), Research Assistant
Melinda Kyloh, Technical Assistant

Students

Simona Carbone, BSc (Hons), PhD student
Tim Hibberd, BHlthSc (Hons), PhD student

Contacts

Prof Simon Brookes

Ph: (08) 8204 4201 Int Ph: +61 8 8204 4201 Fax: (08) 8204 5768 Int Fax: +61 8 8204 5768 Email: simon.brookes@flinders.edu.au

Research Projects

• Sensation from Upper Gut
• Pain Sensation
• Sensation from the Distal bowel
• Sensory innervation of the Bladder
• Innervation of human gut

Collaborative Research

Our collaboration with the laboratory of Dr A Blackshaw ( Royal Adelaide Hospital) on afferent nerves in mouse gut in health and inflammation has continued.

Our long-standing collaboration with Assoc Prof D Wattchow (Dept of Surgery, Flinders University) continues. We have worked together for many years applying techniques developed in animal tissue to study the neuroanatomy of the human gut and most recently to human blood vessels.

Media Appearances

• SJH Brookes. ABC Radio, Adelaide, interview with Sarah Aitken, 13/3/08.
• Costa. Cortex values; neuroeconomics (“Grey Matters” column), Fast Thinking, Autumn 2006 pg 30-33
• M Costa. Good to the Bone; biological bases of morality (“Grey Matters” column), Fast Thinking, Spring 2006 pg 21-23
• M Costa. The Clock in your Head; brain and time (Special Feature), Fast Thinking, Summer 2006 pg 55-58

Publications

Song X, Chen BN, Zagorodnyuk VP, Lynn PA, Blackshaw LA, Grundy D, Brunsden AM, Costa M, Brookes SJ (2009) Identification of medium/high-threshold extrinsic mechanosensitive afferent nerves to the gastrointestinal tract. Gastroenterology 137(1): 274-84, 284.e1

Wattchow DA, Brookes SJH, Murphy EM, Carbone S, De Fontgalland D and Costa M (In press) Regional variation in the neurochemical coding of the myenteric plexus of the human colon and changes in patients with slow transit constipation. Neurogastroenterology and Motility

Zagorodnyuk V, Gibbins I, Costa M, Brookes S & Gregory S (2008) How many sensors in the bladder? Physiology News, 73:18-20

Spencer NJ, Kerrin A, Zagorodnyuk VP, Hennig GW, Muto M, Brookes SJH, McDonnell O (2008) Identification of functional intramuscular rectal mechanoreceptors in aganglionic rectal smooth muscle from piebald lethal mice. Am J Physiol Gastrointest Liver Physiol, 294(4) G855-867 (IF:3.761)

De Fontgalland D, Wattchow, DA, Costa M and Brookes SJH (2008) Immunohistochemical characterisation of the innervation of human colonic mesenteric and submucosal blood vessels. Neurogastroenterology and Motility, 20(11):1212-1226 (IF: 3.364)

Brookes SJ, Zagorodnyuk VP, Lynn PA, Song X, Chen N, Olsson C, Costa M (2008) Structural basis of sensory nerve pathways from the gut. European Review for Medical & Pharmacological Sciences, 12 Suppl 1:132-3

Brunsden AM, Brookes SJ, Bardhan KD and Grundy D (2007) Mechanisms underlying mechanosensitivity of mesenteric afferent fibers to vascular flow. Am J Physiol Gastrointest Liver Physiol 293(2):G422-8

Zagorodnyuk VP, Gibbins IL, Costa M, Brookes SJH and Gregory SJ (2007) Properties of the major classes of mechanoreceptors in the guinea pig bladder. The Journal of Physiology 585(1):147-163

Murphy EM, De Fontgalland D, Costa M, Brookes SJ, Wattchow DA. (2007) Quantification of subclasses of human colonic myenteric neurons by immunoreactivity to Hu, choline acetyltransferase and nitric oxide synthase. Neurogastroenterol Motil. 19(2):126-34

Blackshaw LA, Brookes SJ, Grundy D, Schemann M. (2007) Sensory transmission in the gastrointestinal tract. Neurogastroenterol Motil. 19(1 Suppl):1-19. Review

Costa M (2006) Advances in Sensors; The Lessons from Neurosciences. In: Advances in Sensing with Security Applications, ed: Byrnes J. Springer. 55-67

Costa M (2006) All together now: from pacemakers to gastric peristalsis. Journal of Physiology, 571.1:1

Olsson C, Chen BN, Jones S, Chataway TK, Costa M and Brookes SJH (2006) Comparison of extrinsic efferent innervation of guinea pig distal colon and rectum. Journal Of Comparative Neurology 496(6):787-801

Brookes SJH and Costa M (2006) Functional Histoanatomy of the Enteric Nervous System. In: Physiology of the Gastrointestinal Tract (4th ed) ed: LR Johnson, Elsevier, Chapter 21 577-602

Yang X, Liu R and Brookes SJH (2006) Intraganglionic laminar endings act as mechanoreceptors of vagal afferent nerve in guinea pig esophagus. Acta Physiol Sinica 58(2) 171-176 (Corrigendum of authorship published in 2007 Acta Physiol Sinica 59(5):627 (also known as Shengli Xuebao. 59(5). Oct 25 2007 p627)

Zagorodnyuk VP, Costa M and Brookes SJH (2006) Major classes of sensory neurons to the urinary bladder. Autonomic Neuroscience -Basic & Clinical 126:390-397

Costa M, Sanders KM, Schemann M, Smith TK, Cook IJ, de Giorgio R, Dent J, Grundy D, Shea-Donohue T, Tonini M, Brookes SJH: (2005) A teaching module on cellular control of small intestinal motility. Neurogastroenterol & Motil 17 (Suppl 3): 4-19

Shea-Donohue T, Cook IJ, de Giorgio R, Tonini M, Dent J, Costa M, Grundy D, Sanders KM, Schemann M, Smith TK, Brookes SJH: (2005) A teaching module on irritable bowel syndrome. Neurogastroenterol & Motil 17 (Suppl 3): 20-40

Costa M: (2005) Advances in Sensors; The Lessons from Neurosciences. In: Advances in Sensing with Security Applications Vol 2, edited by Byrnes J, Springer

Brookes SJH, Cook IJ, Costa M, de Giorgio R, Dent J, Grundy D, Sanders KM, Schemann M, Shea-Donohue T, Smith TK, Tonini M: (2005) Education project for pathophysiology of gastrointestinal. Neurogastroenterol & Motil 17 (Suppl 3): 2-3

Brookes SJH and Costa M: (2005) Functional Histoanatomy of the Enteric Nervous System. In; Physiology of the Gastrointestinal Tract (4th Ed) Ed: LR Johnson

Lynn PA, Zagorodnyuk VP, Hennig GW, Costa M and Brookes SJH: (2005) Mechanical activation of rectal intraganglionic laminar endings. J Physiol (Lond) 564.2:589-601

Zagorodnyuk VP, Lynn PA, Costa M and Brookes SJH: (2005) Mechanisms of mechanotransduction by specialised low threshold mechanoreceptors in the guinea pig rectum. Am J Physiol Gastrointest & Liver Physiol 89:397-406

Brookes, SJH, Zagorodnyuk VP and Costa M: (2005) Mechanotransduction by vagal tension receptors in the upper gut. In: Advances in Vagal Afferent Neurobiology, edited by Bradley J. Undem and Daniel Weinreich. CRC Press

Cook IJ and Brookes SJH: (2005) Motility of the Large Intestine. Chapter 86, Sleisenger & Fordtrans’ Gastrointestinal & Liver Disease 8th Edition, in press

Bright T, Kapoor R, Voyvodich F, Schloithe A, Wattchow D: (2005) The use of a balloon catheter to improve evaluation in anorectal manometry. Colorectal Dis. 7(1):4-7

Ryan MD, Wattchow D, Walker M, Hakendorf P: (2004) Adhesional small bowel obstruction after colorectal surgery. ANZ J Surg. 74(11):1010-2

Hollington P, Neufing P, Kalionis B, Waring P, Bentel J, Wattchow D, Tilley WD: (2004) Expression and localization of homeodomain proteins DLX4, HB9 and HB24 in malignant and benign human colorectal tissues. Anticancer Res. 24(2B):955-62

Brookes SJH and Costa M (2004). “Functional Neuroanatomy” in: Pathophysiology of the Enteric Nervous System, ed: Grundy D and Spiller R, Publ: Blackwell

Costa M, Brookes SH, Zagorodnyuk V: (2004) How many kinds of visceral afferents? Gut. 53 Suppl 2:ii1-4. Review

Berthoud HR, Blackshaw LA, Brookes SJ, Grundy D: (2004) Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterol Motil. 16 Suppl 1:28-33. Review

Olsson C, Costa M, Brookes SJ: (2004) Neurochemical characterization of extrinsic innervation of the guinea pig rectum. J Comp Neurol. 470(4):357-71

Zhang L, Jones S, Brody K, Costa M, Brookes SJ: (2004) Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse. Am J Physiol Gastrointest Liver Physiol. 286(6):G983-91

Smith TK, Oliver GR, Hennig GW, O’Shea DM, Vanden Berghe P, Kang SH, Spencer NJ (2003) A smooth muscle tone-dependent stretch-activated migrating motor pattern in isolated guinea-pig distal colon. J Physiology 551(pt 3): 955-69

Zagorodnyuk VP, Chen BN, Costa M, Brookes SJ: (2003) Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea pig oesophagus. J Physiol 553(pt2): 575-87

Lynn PA, Olsson C, Zagorodnyuk V, Costa M, Brookes SJ (2003) Rectal intraganglionic laminar endings are transduction sites of extrinsic mechanoreceptors in the guinea pig rectum. Gastroenterology 125(3):786-94

Spencer NJ, Hennig GW, Smith TK (2003) Stretch-activated neuronal pathways to longitudinal and circular muscle in guinea pig distal colon. Am J Physiol Gastrointest Liver Physiol. 284 (2): G231-41

Zagorodnyuk VP, Chen BN, Costa M and Brookes SJH. (2002) 4-aminopyridine- and dendrotoxin-sensitive potassium channels influence excitability of vagal mechano-sensitive endings in guinea-pig oesophagus. British Journal of Pharmacology 137 1195-1206

Spencer, NJ, Hennig GW, Smith TK. (2002) A rhythmic motor pattern activated by circumferential stretch in guinea-pig distal colon. J. Physiol. 545(2), 629-648

Brookes SJH and Costa M. (2002) Cellular organisation of the mammalian enteric nervous system. In: Innervation of the Gastrointestinal Tract. Editors: Brookes SJH and Costa M.: Publ: Taylor and Francis, London & UK

Porter AJ, Wattchow DA, Brookes SJH and Costa M. (2002) Cholinergic and nitrergic interneurons in the myenteric plexus of the human colon. Gut 51 70-75

Spencer NJ, Hennig GW, Smith TK. (2002) Electrical rhythmicity and spread of action potentials in longitudinal muscle of guinea-pig colon. Am J Physiol 282(5), G904-1

Zagorodnyuk VP, D'Antona G, Brookes SJH and Costa M. (2002) Functional GABAb receptors in the guinea-pig nodose ganglion neurones. Autonomic Neuroscience: Basic and Clinical 102 20-29

Brookes SJH and Costa M. (2002) Innervation of the Gastrointestinal Tract. Series: The Autonomic Nervous System; Series Editor: Burnstock G; Publ: Taylor and Francis, London & UK

Cook IJ and Brookes SJH. (2002) “Motility of the Large Intestine”, Chapter 86, Sleisenger & Fordtrans’ Gastrointestinal & Liver Disease 7th Edition. 1679-1691

Costa M, Wattchow and Brookes SJH. (2002) Neuronal control in gastrointestinal disease. Eur. J Surgery, 168, 39-46

Hennig, GW, Smith, CB, Smith TK. (2002) Patterns of intracellular and intercellular Ca2+ waves in the longitudinal muscle layer of the murine large intestine in vitro. J Physiol. 543(1), 233-53

Spencer, NJ, Hennig GW, Smith, TK. (2002) Properties of stretch-activated intrinsic neuronal pathways to longitudinal and circular muscle in guinea-pig distal colon. Am. J. Physiol.

Abdu, F, Hicks, GA, Hennig, GW, Allen, J, Grundy, D. (2002) Somatostatin SST(2) inhibit peristalsis in the rat and mouse jejenum. Am J Physiol 282(4), G624-33

Berthoud, HR, Hennig, G, Campbell, M, Volaufova, J, Costa, M. (2002) Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs. Neurogastroenterol. Motil. 14(6), 677-688

Koukorou A, Lyon W, Rice J, Wattchow DA. (2001) A prospective randomised trial of polypropylene mesh compared with nylon darn in inguinal hernia repair. British Journal of Surgery. 88(7):931-934

D'Antona G, Hennig GW, Costa M, Humphreys CM and Brookes SJH: (2001) Analysis of motor patterns in the isolated guinea-pig large intestine by spatio-temporal maps. Neurogastroenterology & Motility 13(5): 483-492

Brookes SJH (2001) Classes of enteric nerve cells in the guinea-pig small intestine. Anat Rec 1;262(1):58-70

Simula ME, Brookes SJH, Meedeniya ACB, Toouli J and Saccone GTP: (2001) Distribution of nitric oxide synthase and vasoactive intestinal polypeptide immunoreactivity in the sphincter of Oddi and duodenum of the possum. Cell & Tissue Research 304(1): 31-41

Zagorodnyuk VP, Chen BN and Brookes SJH: (2001) Intraganglionic laminar endings are mechano-transduction sites of vagal tension receptors in the guinea-pig stomach. Journal of Physiology-London. 534(1): 255-268

Yuan SY, Costa M, Brookes SJH (2001) Neuronal control of the pyloric sphincter of the guinea pig. Neurogastroenterol Motil 13(3):187-98

Brookes SJH, D'Antona G, Zagorodnyuk VP, Humphreys CMS and Costa M. (2001) Propagating contractions of the circular muscle evolked by slow stretch in flat sheets of guinea-pig ileum. Neurogastroenterology and Motility 13(6): 519-531

Brookes SJH (2001) Retrograde tracing of enteric neuronal pathways. Neurogastroenterol Motil 13(1):1-18

Costa M, Brookes SJH, Hennig GW: (2000) Anatomy and physiology of the enteric nervous system. Gut 47(Suppl 4): 15-19

Costa M: (2000) Concluding remarks. Gut 47(Suppl 4): 88

Brookes SJH and Zagorodnyuk VP: (2000) Intraganglionic laminar endings are transduction sites of stretch-sensitive vagal mechanoreceptors in the guinea-pig esophagus. Gastroenterology 18:4, 995

Curro D, Costa M, Brookes SJH: (2000) Motor activity of the guinea-pig ileum induced by maintained distension and cyclooxygenase inhibition. Gastroenterology 18: 4, 3665

Zagorodnyuk VP, Brookes SJH: (2000) Transduction sites of vagal mechanoreceptors in the guinea pig oesophagus. Journal of Neuroscience 20(16): 6249-6255

Updated December 15, 2009