Mechanisms Controlling The Excitability Of Corneal Nociceptor Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$364,759.00
Summary
The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that ar ....The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that are uniquely expressed in pain sensing nerves. These channels have been hypothesised to play an important role in determining the behaviour of these nerves. In addition, the project investigates how some substances released in inflamed tissues sensitize pain sensing nerves, causing them to more readily discharge action potentials. This change is the major cause of pain associated with inflammatory diseases such as arthritis. In summary, the proposed project will provide new insight into how pain sensing nerves function. This knowledge is essential for the development of more effective strategies for treating pain resulting from inflamed and damaged tissue.Read moreRead less
Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitiv ....Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often accepted or taken for granted. The outcome of this work will be an increased understanding of the way in which nerve injury leads to spontaneous pain and increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
A Molecular Approach To Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
Neural Mechanisms Underlying Human Grasp And Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$396,100.00
Summary
We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well ....We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well as in other neurological diseases such as neuropathies, nerve injuries, cerebral palsy and many others. The broad aim of this study is to investigate the poorly understood neural mechanisms that underlie sensorimotor control of hand function. We will target a specific aspect of manual dexterity that is crucial for the execution of common everyday tasks, like pouring liquid from a bottle, in which the digits are subjected to torsional loads. In order to maintain stable grasps, the motor control system must rapidly and automatically adjust the grip forces employed to meet the demands imposed by the changing torsion. This is only possible because of sensory feedback from the hand, a large component of which arises from the cutaneous mechanoreceptive afferent fibres. In the first two years we will use a combined approach of neural recording from peripheral nerves in anaesthetised monkeys and psychophysics experiments in normal humans to answer the general question: how does the population of cutaneous afferents provide precise feedback about torsion on the digits? In the third year we will perform key experiments in humans, using microneurography to record from their peripheral nerves. This will establish any differences between human and monkey mechanoreceptors.Read moreRead less
Interactions Of Gastric Hormones With Vagal Afferent Pathways And The Role Of This System In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$550,918.00
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 this project aims to find out how to correct this problem in this modern day epidemic.
Cellular Mechanisms Underlying The Sense Of Balance
Funder
National Health and Medical Research Council
Funding Amount
$192,960.00
Summary
Dizziness, vertigo, and imbalance are major reasons for visits to the doctor, particularly by the elderly. For example, balance related falls account for an astonishing 50% of accidental deaths in people over 65. Inner ear disturbances account for 85% of these cases. Illness, infections, disease, head trauma or simply the natural aging process cause these disturbances and it is thought that they result in abnormal signals being sent from the inner ear to the brain. In spite of the health costs a ....Dizziness, vertigo, and imbalance are major reasons for visits to the doctor, particularly by the elderly. For example, balance related falls account for an astonishing 50% of accidental deaths in people over 65. Inner ear disturbances account for 85% of these cases. Illness, infections, disease, head trauma or simply the natural aging process cause these disturbances and it is thought that they result in abnormal signals being sent from the inner ear to the brain. In spite of the health costs associated with disorders of balance, very little is known about how signals are generated in our vestibular organs, let alone what abnormal changes may occur. Our attempts to understand balance in humans have been hampered by the lack of suitable experimental models. This proposal takes advantage of a newly developed mouse preparation to study key problems that could not be realistically addressed in whole animal or dissociated cells. We will investigate three critical components of balance organs. These components are: 1) hair cells that detect motion; 2) nerve endings that send information from hair cells to the brain; and 3) nerve endings that bring information from the brain. The aim of this proposal is to understand how these components interact with each other to provide us with a sense of balance. This knowledge will be the first of its kind and contribute significantly to our understanding of human vestibular function and pathology.Read moreRead less
Defining The Role Of EphA5 In Olfactory Axon Growth, Guidance And Fasciculation
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. In addition, we will also examine the behaviour of live cells as they are growing. In the past all attempts to understand how nerve cell connections are formed in the olfactory system have used dead tissue that has been permanently preserved. In this project we have the unique opportunity to visualise living nerve cells to enable us to determine how the cells react to the guidance signals. The advantage of this approach is that it allows us to identify important interactions as they occur, rather than attempting to decipher them after they have occurred. An analogy would be watching a football game live and observing how goals were scored and appreciating the performance of individual players versus trying to guess from the final score how the game was played and who the key performers were. The results of these experiments will provide important information on the regeneration of olfactory nerve cells, as well as on the initial growth and targeting of these nerve cells.Read moreRead less
I am a neuroscientist interested in injury to the nervous system with emphasis on promoting functional recovery and clinical translation. Injury models are neurotrauma, the long-term effects of maternal drug administration on offspring and diabetic retino
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less