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
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.
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
A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Integrative Role Of Feedback Projections To Cat Primary Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$293,321.00
Summary
Although in the last decade termed The Decade of the Brain we have learned a lot about the brain, the gaps in our understanding of brain functions are still enormous. The analysis of information in the sensory parts of the brain appears to be arranged in a distributed - hierarchical way. For example, different types of nerve fibres leaving the eye carry fairly generalised information about the external visual world along distinct parallel information channels. By the time the signals reach cereb ....Although in the last decade termed The Decade of the Brain we have learned a lot about the brain, the gaps in our understanding of brain functions are still enormous. The analysis of information in the sensory parts of the brain appears to be arranged in a distributed - hierarchical way. For example, different types of nerve fibres leaving the eye carry fairly generalised information about the external visual world along distinct parallel information channels. By the time the signals reach cerebral cortex there is a dramatic increase in complexity of visual stimuli to which cells respond (orientation, length and direction of movement of contours became important). There are at least two parallel feedforward information processing streams across the cerebral cortex involving a number of relay stations at each of which there are further specializations. For example, cells in one area appear to respond only to faces while in some other areas cells respond to motion in particular directions almost irrespective of the position of the stimuli. In the human there are more than 30 visual cortical areas. What is very surprising that from all these areas there are extensive feedback pathways running back to the lower-order areas. The feedback pathways appear to largely criss-cross different information processing streams and their function is very poorly understood. We will record from cells in lower-order areas noting the way they respond to different stimuli. Then we will block the feedback pathway from a particular higher-order area by cooling the area to about 10oC. We have confirmed that this prevents nerve impulses leaving the cooled area. Then we repeat our tests on the cell in the lower-order area. Comparing the responses with and without feedback activity will tell us what the feedback is doing. Understanding the function of feedback pathways hopefully would help us to understand the mechanisms underlying some subtle psychoneurological diseases.Read moreRead less