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
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
Olfactory Ensheathing Cells: A Major Contributor To Axon Guidance?
Funder
National Health and Medical Research Council
Funding Amount
$575,749.00
Summary
The olfactory (smell) system is a unique part of the nervous system because nerve cells are generated throughout life. Understanding how the olfactory system grows and regenerates may lead to therapeutic approaches to repair other regions of the nervous system. This project will use high resolution digital time-lapse imaging of living nerve cells and the specialised cells called olfactory ensheathing cells to determine how the behaviour of these cells can be manipulated to improve regeneration.
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
Development And Plasticity Of The Visual Cortex: An Anatomical And Functional Study
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
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 aim of this project is to investigate the way in which the multiple visual areas of the brain develop and become 'wired' together, and determine how the brain can successfully compensate for damage to these areas.
Headache Prophylaxis By Cortico-brainstem Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$616,437.00
Summary
In this project we hope to discover the cause of migraine headache. Many triggers lead to migraine, but we do not know how. We believe the triggers produce a defect in pain control by the brainstem, which normally keeps sensation from the head below the pain threshold. In migraine, trigger factors acting high in the brain open a pain control gate lower in the brain, producing a migraine headache. If we can prove this, we can develop therapies that will prevent migraine before it starts.
Orientation-specific Contextual Modulation In Human Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$290,413.00
Summary
Context has a strong infuence on our visual perception. We will study patterns of activity in the normal human brain to identify the cortical signature of contextual modulation in vision. The correspondences between patterns of brain activity and visual perception in the normal human brain will provide data against which brain activity in disorders such as schizophrenia and bipolar disorder can be assessed.
Using Contextual Effects To Test Theories Of Coding In Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$200,500.00
Summary
The visual cortex is the main structure in the brain that processes the visual scene. Cells in the cortex respond selectively to features of the scene such as the orientation of objects, the direction they move and their brightness relative to the background. Cortical cells are arranged in a topographic map of visual space, so that nearby cells respond to light from nearby parts of the image. Recent advances have shown that cells talk to each other so a stimulus in one part of the visual field c ....The visual cortex is the main structure in the brain that processes the visual scene. Cells in the cortex respond selectively to features of the scene such as the orientation of objects, the direction they move and their brightness relative to the background. Cortical cells are arranged in a topographic map of visual space, so that nearby cells respond to light from nearby parts of the image. Recent advances have shown that cells talk to each other so a stimulus in one part of the visual field can influence the responses of cells looking at other regions. This communication between cells is important in guiding the brain to focus on areas of the visual scene that are most important, a process known as attention. An example would be that a mouse moving through the periphery of someone's vision would attract their attention away from objects elsewhere in the scene. This project is designed to study the way that cells in the visual cortex cooperate to guide attention. Attention is important because it reduces the need to process all the detail in the visual scene with the same level of accuracy, leaving more resources free to process what is important. Attention deficits are a problem for people with dyslexia, so understanding the physiological basis of attention is an important goal. As well as attention, the visual system has a range of other mechanisms to select important information from the visual scene. For example, visual adaptation tends to improve the ability to code changes in the visual scene at the expense of reducing the sensitivity of the system overall. This project will investigate the relationship between attentional and adaptive mechanisms in the visual cortex. We expect to establish the precise physiological mechanisms that drive adaptive and attentional mechanisms in the mammalian brain.Read moreRead less
Neurosteroid Modulation Of GABA-inhibition In Vivo: Central Auditory Pathway Models
Funder
National Health and Medical Research Council
Funding Amount
$331,650.00
Summary
All neurons at higher levels of the central nervous system signal in response to the outcome of various excitatory and inhibitory inputs (synapses) from other neurons. Most of the fast-acting inhibition is mediated by chloride ion influx through a channel which is gated by the neurotransmitter GABA. Termed the GABAa-receptor, this channel is known to be modulated by a wide range of pharmacological agents (e.g. valium; ethanol, many anaesthetics) which may enhance or suppress its efficacy. There ....All neurons at higher levels of the central nervous system signal in response to the outcome of various excitatory and inhibitory inputs (synapses) from other neurons. Most of the fast-acting inhibition is mediated by chloride ion influx through a channel which is gated by the neurotransmitter GABA. Termed the GABAa-receptor, this channel is known to be modulated by a wide range of pharmacological agents (e.g. valium; ethanol, many anaesthetics) which may enhance or suppress its efficacy. There are also good reasons for concluding that there is a capacity for modulation by endogenous substances. Brain synthesized steroids (neurosteroids) are known to have a potent enhancement effect upon the efficacy of GABAa-receptors, and have been implicated in a number of clinical situations, including menstrual cycle related depression. Work of others has shown that rapid synthesis of neurosteroids acts to increase inhibition in response to anxiety-inducing stimuli. Our recent work has shown that neurosteroids mediate an induced increase in inhibition in the auditory midbrain area. A surprising aspect of that study was that neurosteroids also appear to mediate ongoing levels of inhibition. This now allows us to use the many inhibitory interactions in the auditory pathway as potential models for studying the role of neurosteroid modulation of GABA inhibition in normal brain function. This is important because a number of medical treaments have the side effect of changing the synthesis of neurosteroids. We will also use an auditory system model of neurotrauma to examine the role of neurosteroids in increasing inhibition (to counter a potentially lethal increase in excitability). The work will involve electophysiological functional measurements and the development of highly sensitivity analytical protocols using an electrospray mass spectrometer for direct measurement of neurosteroids in submicrogram samples of brain tissue.Read moreRead less