The human brain has many subdivisions (�areas�) that are dedicated to vision, but in many cases their functions remain unclear. This project will study an area located deep in the brain, about which very little is known, and which appears to be affected from early stages in conditions such as Alzheimer�s disease. By understanding the patterns of electrical activity of cells in this region, and their connections with other brain areas, we hope to decipher their contribution to sensory cognition.
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.
Analysis Of Functional Role Of The BDNF Precursor In Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve ....Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve via its receptors and whether it plays any role in the development of pain and maintenance of neuropathic pain after nerve injury. Successful execution of the project will eludicate mechanisms of pain, especially neuropathic pain, and will provide important information to assist in the design of drugs for neurological diseases.Read moreRead less
Mechanisms Of Activation Of Vascular Afferent Nociceptors To The Gut
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
We have recently identified the nerve fibres responsible for detecting pain from the gut. In this project we will study exactly how these nerve cells are activated by movements of the gut wall, by changes in blood vessel diameter and how this can be studied most efficiently We will use this information to develop simple preparations in which to study these sensory nerves in animal and adult tissue to test which drugs may affect their excitability and hence be useful in treating gut pain.
The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells w ....The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells which line the back of the eye). It is characterised by a very high density of cone photoreceptors, and is essential for high-acuity vision. This makes the fovea the most important part of the primate retina, but the high density of nerve cells there is thought to be the reason why the fovea is especially vulnerable to disease and age-related degeneration. Our aim is to analyse, using high-resolution microscopic techniques, the connections of koniocellular-pathway cells within the retina. We specifically aim to discover whether the koniocellular pathway contributes to foveal vision. Recent work from our and other laboratories has shown that many koniocellular-pathway cells receive functional connections from short-wavelength sensitive (blue) cone photoreceptors. Thus, our study will provide new insights into the connectivity of blue-cone pathways in the fovea. Although these experiments address basic scientific questions, they can lead to improved clinical practice. Understanding the wiring diagram of the retina can inform clinical studies of conditions such as glaucoma, and helps to give a rational basis for development of treatments. For example, dysfunction in blue-cone pathways is an early sign of glaucoma, so understanding the connections of blue-cone pathways in the fovea can lead to improved methods for early detection of this leading cause of blindness.Read moreRead less
The retina lines the back of the eye and sends multiple movies of the visual world to the brain. This project aims to investigate how these multiple information channels are created. Descriptions of the basic pattern of wiring in the healthy retina will help clinical researchers to understand the disruptions that occur in visual disease. The precision of normal retinal wiring also delineates the precision required to restore normal function to a diseased or degenerating eye.
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Hearing Protection Conferred By P2X2 Receptor Signaling In The Cochlea
Funder
National Health and Medical Research Council
Funding Amount
$580,019.00
Summary
Hearing loss from noise damage and ageing is the principal sensory disability in our society. This project will determine the contribution of the P2X2 receptor to protection from noise-induced hearing loss. We have found that P2X2 knockout mice have minimal temporary threshold shift. We will investigate the physiological basis for this and determine why this mouse model has greater hearing loss with intense sound and faster age-related hearing loss compared with wildtype controls.