Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
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 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
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain devel ....Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain develop and become 'wired' together in the period following birth. We will also determine if there are mechanisms which allow alternate routes to be found for processing visual information while the brain is still establishing connections between its multiple areas. This will allow us to understand the anatomical and physiological bases of the deficits caused by early damage to the visual areas of the brain, and perhaps point to strategies that will lead to improved recovery of visual function.Read moreRead less
Understanding The Role Of The Olfactory Ensheathing Cell In The Olfactory Sensory System
Funder
National Health and Medical Research Council
Funding Amount
$494,000.00
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 how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. Information we obtain about how this system develops and regenerates may be useful in treating brai ....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 how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. 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 how olfactory nerve cells interact with the ensheathing cells. We will use transgenic mice in which the different cells are marked by separate colours which will allow us to easily identify the cells and see where they grow. 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 interact with the ensheathing cells. 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. These experiments will provide important information about how the olfactory ensheathing and nerve cells grow and regenerate.Read moreRead less
Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
Training-induced Restoration Of Topographic Maps And Vision During Opticnerve Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$379,725.00
Summary
The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, h ....The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, however, over the last decade is the recognition that the adult CNS, particularly after damage, does have a capacity for repair and that appropriate neural activity, produced either via relevant experience or specific training, is essential in driving the repair process to produce useful behavioural recovery. One of the clearest examples comes from our laboratory in which we have recently shown that training animals on specific visual tasks during optic nerve regeneration allows useful vision to be restored; untrained animals are blind via the experimental eye. The advantage of the visual system is that it is a relatively simple part of the CNS with one major class of nerve cell projecting to well defined and accessible brain regions. The significance of the project is that, for the first time, we are able pinpoint specific training-induced effects within identified nerve cells and their connections, a task that is much harder within other CNS regions. In particular, we will examine molecular, anatomical and functional changes that are induced via training and explore whether intervention with blockers of inhibitory neurotransmission further improves the beneficial effects of training. Understanding the changes in nerve cells that underlie the positive effects of training after neurotrauma will have implications for the continuing development of rehabilitation strategies for improved recovery after CNS injury.Read moreRead less
Functional Anisotropies In The Processing Of Orientation And Direction-of-motion By Human Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$366,164.00
Summary
We will study patterns of activity in the human brain to identify the cortical signature of normal visual function. The correspondences between patterns of brain activity and the structure and motion of the visual image in the normal human brain will provide data against which brain activity in a range of disorders from amblyopia to schizophrenia can be assessed.
Understanding The Role Of Regulatory T Cells In Chronic Pain Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$587,046.00
Summary
Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for ....Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for pain management.Read moreRead less
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
The superior colliculus is a brain centre which uses visual information from the eyes and other sensory information, such as sound, to direct the head and eyes towards objects of interest. This project will use current advancements in optogenetics to activate connections to this brain region in order to understand its role in coordinating head and eye movements. This will advance our understanding of how the brain collects and processes visual information to subserve behavioural functions.
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less