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Enjoyable Gut Neuroscience
Research
Our laboratory is primarily a Neurophysiology lab investigating Sensory Transduction and Synaptic Transmission. We investigate how the gastrointestinal tract senses lumenal contents and initiates the correct reflex or motor program. These actions are controlled by a complex intrinsic system of nerves present within the wall of the gut. These nerves are called the enteric nervous system (ENS) which contains about as many neurons as are present inthe spinal cord. The ENS contains all the components of a reflex arc: sensory neurons, interneurons and motor neurons.
In our laboratory, we are investigating the role of non-neuronal cells in relaying lumenal sensory stimuli - such as acid, touch, or noxious chemicals - to enteric sensory nerve terminals via the graded release of transmitters such as serotonin (5-HT) or ATP. We are also investigating how the enteric neurons talk to each other under stressful conditions such as inflammation or obesity. Our methods include electrophysiological recording from single neurons, neuropharmacological analysis of responses in neurons and in the whole organ, modulation of intracellular signal transduction pathways, and electrochemical detection of 5-HT release from nerve terminals.
Current Research Projects
Project 1 (ILP/Hon/PhD) Characterization of 5-HT release from intact gastrointestinal tract
Collaborators: Dr Xiaochun Bian, Dr Alan Lomax and Dr Rebecca Bertrand
Description: This project is characterising the release of 5-HT (serotonin; 5-hydroxytryptamine) from the gastrointestinal neuroendocrine cells known as enterochromaffin cells (EC cells). Evoked release of 5-HT from EC cells is a critical step in the sensory transduction of chemical and mechanical information from the lumen of the gut. Alterations in the synthesis, storage or release of 5-HT can cause or exacerbate disease (e.g., Coates et al., 2004). Despite this, little is known about how EC cells respond to stimuli and how 5-HT is released from the intact organ. This project will use a novel electrochemical technique to measure 5-HT release selectively, from intact preparations of small and large intestine, and in real-time. The control of release by ligand-gated and G-protein coupled receptors will also be investigated.
The first project aims to characterise serotonin release from the intestinal epithelium. Techniques involve making electrochemical recordings with carbon fibre electrodes and pharmacological manipulation of neurotransmission and of calcium channels. The investigation may then diverge to study serotonin release from single cells correlated with the activity of single sensory neurons, or to study release from the whole organ during motor reflexes.
Project 2 (ILP/Hon/PhD) Development of sensors to detect 5-HT release in human bowel disease
Collaborators: Prof Steven Vanner, Dr Mike Beyak, Dr Lu Liu and Dr Rebecca Bertrand
Description: In Inflammatory Bowel Disease (IBD) or functional bowel disorders such as Irritable Bowel Syndrome (IBS), there are profound changes in the content, release and reuptake of 5-HT (i.e., 5-HT metabolism). This project will look at the release of 5-HT on the same time scale that it is occurring and at the site of action in the intestinal lumen. For this purpose, a new sensor will be developed that has the potential to be embedded in an experimental endoscope suitable for use in patients. Because we have amassed significant data using traditional carbon fibre electrodes, we have a unique opportunity to compare this with data from any newly developed sensor.
Project 3 (ILP/Hon/PhD) Isolation of EC cells and crypts to examine the biophysics of 5-HT release
Collaborators: Dr Lu Liu and Dr Rebecca Bertrand
 Description: In this project, we will investigate the regulation of 5-HT release from EC cells using state-of-the-art electrochemical methods combined with pharmacological and neurophysiological tests. This will allow us to investigate the control of 5-HT release in real-time, at the site of action and from only a few EC cells. We will record 5-HT release a) from in vitro preparations (where the EC cells have their normal complement of receptors and ion channels), b) from isolated crypts (containing only a few EC cells which have been minimally disrupted) and c) from enriched populations of dispersed EC cells (where single EC cells can be examined, but cell receptor/channel complements may be changed). In each condition, one or two small carbon fibre electrodes will be used to record from only a few intestinal EC cells at a time. We will compare the properties of release in these three paradigms by looking at time course, rundown and summation of 5-HT release events and by looking at control of release by blocking voltage-gated ion channels. This will allow us to determine whether 1) these preparations are physiologically equivalent and 2) whether there are distinct, functional sub-populations of EC cells.
Project 4 (ILP/Hon/PhD) The role of 5-HT7 receptors in synaptic transmission in the ENS
Collaborators: Dr Rebecca Bertrand
Description: 5-HT is produced by the body from tryptophan, a dietary amino acid found, for example, in bananas. It is used as a neurotransmitter in the brain and periphery and is also used by platelets to help with the clotting reaction of blood. There are up to 15 subtypes of 5-HT receptor found in the body, many with very specific functions. The 5-HT7 receptor has been found to play a role in thermoregulation in the CNS, and recently, we've shown that it may be responsible for the excitatory effects of 5-HT on the intrinsic sensory neurons located in the gastrointestinal tract. The receptor mediating these effects of 5-HT on the enteric neurons has been the subject of controversy for the last 30 years.
This project aims to characterise the purine and serotonin receptors present on the cell bodies of the intestinal sensory neurons. Techniques involve electrophysiological recording from single sensory neurons, pharmacological characterisation of receptor subtypes and microdissection.
Staff
Dr Rebecca L Bertrand, BSc (Hon), PhD (UMelb) | research interests
Sevvandi Senadheera, BSc, MSc, (Hon, UAuck) Senior Research Assistant/part-time PhD (with Dr Shaun Sandow)
Irit Markus, Senior Research Assistant (p/t with Dr Lu Liu)
Youngsoo Kim (PhD candidate; co-supervised by Prof Gary Housley, Dr Andrew Moorhouse)
Niloufer Johansen (PhD candidate; Primary supervisor A/Prof James Brock - POWMRI)
Kai Loon (ILP student)
Mary Grealish (ILP student)
Research Grants
| 2009-13 | NH&MRC Project grant (Bornstein, Thomas, Parry, Bertrand) |
| 2009 | Faculty Research Grant (Bertrand and Liu) |
| 2009 | Ramaciotti Equipment Grant Gift (Bertrand) and Establishment Gift (R Bertrand) |
| 2008-10 | NH&MRC Project grant (Bertrand and Liu) |
| 2004-6 | NH&MRC Project grant (Bertrand) |
| 2003 | NH&MRC equipment grant |
| 2001 | Buckland Foundation, NH&MRC and Ramaciotti equipment grants |
| 2000-3 | NH&MRC RD Wright, Fellowship |
| 2000-2 | NH&MRC Project grant |
| 1995-7 | National Research Service Award (NIH) Fellowship |
Publications
Research papers (2001 to present) For a complete listing, please see PubMed. For PDF's, please goto my Personal Website.
- Bertrand, P. P., Hu, X., Mach, J., Bertrand, R. L. (2008). Serotonin (5-HT) release and uptake measured by real-time electrochemical techniques in the rat ileum. Am J Physiol. 295(6):G1228-36.
- Monro, R. L., Bornstein, J. C. and Bertrand, P. P. (2008). Synaptic Transmission from the Submucous Plexus to the Myenteric Plexus in Guinea-Pig Ileum. Neurogastroenterology and Motility. 20(10):1165-73.
- Bertrand, P. P. and Bertrand, R. L. (2007). Teaching gastrointestinal motility using classic papers by Dr. Walter B. Cannon. Advances in Physiology Education. 31(2): 136-9.
- Bertrand, P. P. (2006). Real-time measurement of serotonin release and motility in guinea pig ileum. Journal of Physiology. 577(2): 689-704.
- Bertrand, P. P., Paranavitane, U. T., Chavez, C., Gogos, A., Jones, M. and van den Buuse, M. (2005). The effect of low oestrogen state on serotonin transporter function in mouse hippocampus: a behavioural and electrochemical study. Brain Research. 1064(1-2): 10-20.
- Monro, R. L., Bertrand, P. P. and Bornstein, J. C. (2004). ATP participates in three excitatory post-synaptic potentials in the submucous plexus of the guinea pig ileum. Journal of Physiology 556(2): 571-584.
- Bian, X.-C., Heffer, L. F., Gwynne, R. M., Bornstein, J. C. and Bertrand, P. P. (2004). Synaptic transmission in simple motility reflex pathways of guinea pig distal colon. American Journal of Physiology 287: G1017-G1027.
- Bertrand, P. P. (2004). Bursts of recurrent excitation in the activation of intrinsic sensory neurons of the intestine. Neuroscience 128(1): 51-63.
- Bertrand, P.P. (2004). Real-time detection of serotonin release from enterochromaffin cells of the guinea pig ileum. Neurogastroenterology and Motility 16(5): 511-514. * A "Hot Topic" with Editorial. Cited as of "Outstanding interest" in Current Opinions in Gastroenterology 2005, 21: 176-182
- Monro, R. L., Bornstein, J. C. and Bertrand, P. P. (2004). 5-HT7 receptors mediate slow synaptic transmission in myenteric AH neurons. Neuroscience 134(3):975-986.
- Bian, X.-C., Bornstein, J. C. and Bertrand, P. P. (2003). Nicotinic transmission at functionally distinct synapses in descending reflex pathways of the rat colon. Neurogastroenterology and Motility 15(2):161-71.
- Monro, R. L., Bertrand, P. P. and Bornstein, J. C. (2002). ATP and 5-HT are the principal neurotransmitters in the descending excitatory reflex pathway of the guinea-pig ileum. Neurogastroenterology and Motility. 14(3):255-264 * 3rd most cited paper in NGM for 2002.
- Bertrand, P. P. and Bornstein, J. C. (2002). ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors. Journal of Neuroscience 22(12): 4767-4775.
- Lomax, A. E. G., Bertrand, P. P. and Furness, J. B. (2001). Electrophysiological characteristics distinguish three classes of neuron in submucosal ganglia of the guinea-pig distal colon. Neuroscience. 103(1): 247-257.
Editorials, Reviews and Book Chapters (2001 to present)
- Bertrand, P. P. and Bian X-C. (2008). From 'macro' to 'micro': mapping the neuronal circuits of the intestine. Clinical and Ex-perimental Pharmacology and Physiology. 35(7):715-6.
- Bertrand, P. P. (2007). Editorial: A new role for P2 receptors: talking with calcium activated potassium channels Neurogastroenterology and Motility. 19(11):865-8.
- Ren, J. & Bertrand, P. P. (2007). Purinergic receptors and synaptic transmission in enteric neurons" In: Purinergic signaling in the gastrointestinal tract. Eds J. J. Galligan and L. A. Blackshaw. Special supplement for the journal: Purinergic Mechanisms. In press.
- Bertrand, P. P. and Thomas, E. A. (2004). Multiple Levels of Sensory Integration in the Intrinsic Sensory Neurons of the Enteric Nervous System. Clinical and Experimental Pharmacology and Physiology. 31(11): 745-755.
- Bertrand, P. P. (2003). ATP and Sensory Transduction in the Enteric Nervous System. The Neuroscientist. 9(4):243-60.
- Bornstein, J. C., Furness, J. B., Kunze, W. A. and Bertrand, P. P. (2002). Enteric Reflexes that Influence Motility. In: "Nervous Control of the Gastrointestinal Tract". (eds M. Costa and S. H. Brookes), pp. 1-55.
For a complete listing, please see PubMed.
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Chief Investigators
Dr Paul Bertrand
Department of Physiology
T (02) 9385 3947
F (02) 9385 1059
E
Personal Research Profile
Personal Website
Dr Rebecca Bertrand
Department of Physiology
T (02) 9385 3947
F (02) 9385 1059
E
Personal Research Profile
Personal Website
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