A novel sensory neural circuit has been identified innervating the airways and lungs. The anatomical organisation of this circuit has been described to some extent in previous studies, however there is a significant gap in knowledge with respect to its functional importance. This project will develop methods to address this knowledge gap and in doing so the project will firstly describe how this circuit controls breathing under normal conditions and secondly how this becomes dysregulated during
How Intestinal Motility Activates Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$555,875.00
Summary
Pain and discomfort from the gut are common and unpleasant. We understand how gut sensory nerve cells work, at the cellular, molecular and genetic level. However, movement of the gut wall and contents are the major cause of activation of sensory neurons. We know little about which particular patterns of movement cause pain. This is crucial information for accurately diagnosing human gut disorders, for monitoring effectiveness of treatments and for identifying potential new drug targets.
Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.Read moreRead less
Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (de ....Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (defecation/urination) functions are coordinated. The expected outcomes are predicted to aid future discovery of mechanisms of cross-organ sensitisation and are anticipated to provide significant benefit to therapy development for chronic visceral pain syndromes associated with bowel and bladder dysfunction.Read moreRead less
How the gut nervous system interacts with bacteria. This project aims to reveal how the enteric nervous system of the gastrointestinal (GI) tract interacts with the gut microbiota. Gut function has largely been studied without considering microbiota. The project will use genetically modified animal models, image analysis of gut motility and sequencing of gut microbes, and develop neurophysiological methods to understand gut function. Expected benefits include better understanding of mechanisms u ....How the gut nervous system interacts with bacteria. This project aims to reveal how the enteric nervous system of the gastrointestinal (GI) tract interacts with the gut microbiota. Gut function has largely been studied without considering microbiota. The project will use genetically modified animal models, image analysis of gut motility and sequencing of gut microbes, and develop neurophysiological methods to understand gut function. Expected benefits include better understanding of mechanisms underlying antibiotic resistance, risks associated with discretionary caesarean sections and the benefits of breastfeeding.Read moreRead less
Mapping the connectome that controls blood pressure. The connections that an individual brain cell receives from other cells ultimately determines its behaviour. Using a revolutionary new technique, the project will create a map of the brain cells that control blood pressure.
Development of sympathetic nerve pathways. The mature nervous system contains many types of neurons connected in precise ways. Developing neurons must make many decisions about what type of neuron to become and what connections to make. This study looks at the mechanisms that guide the developing neurons in these important decisions.
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated ....The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated appreciably in the past. We believe that these sensory neural circuits will reveal important new insights into how internal organs perform their diverse and essential functions to sustain life.Read moreRead less
Wiring the gut's nervous system: formation and maturation of synapses. This project aims to determine how nerve circuits controlling intestinal functions develop; specifically how communication between specific nerve cells is established once they appear in the embryonic gut. It will fill a major hole in existing knowledge of mechanisms regulating the development of normal digestive behaviours.