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
Combining input from vision and hearing greatly enhances perception when information from one of these senses is degraded or incomplete, such as when tracking objects in foggy, dark or noisy places. This enhancement is of considerable importance because degraded input is the daily situation faced by many people with hearing or vision impairment. We will study the neural processes underlying our ability to combine vision and hearing to create a more reliable and accurate perception of the world.
The Role Of Integrins In The Regulation Of Scleral Remodelling During Pathological Myopia Development
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change and this is a complex process, driven by the scleral cells and involving the synthesis of structural components and activity of enzymes which breakdown scleral structure. The aim of this project is to investigate the role of specific scleral proteins (integrins) in high myopia. Integrins reside on the surface of the scleral cells and communicate information about the changes going on in the surrounding sclera. We predict these proteins are important in keeping the cell informed of the local biochemical and biomechanical changes in the sclera and in driving the cell to rapidly adapt to these changes. The project will provide a greater understanding of the process of scleral thinning in high myopia and allow us to test the potential of integrins as therapeutic targets in the sclera, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movement ....One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movements. It is proposed that there are two parallel brain circuits involved in the analysis of motion, one tracking the movement of objects, and the other analysing a person s self-motion. Consider, for example, the task of a tennis player who has to return a serve. In order to achieve this, the brain must precisely integrate information about the ball s motion, as well as information about the player s speed and direction. This requires precise control of eye movements (to keep the eyes on the ball), as well as the ability to control the limb and trunk muscles. The aim of this study will be to map the anatomical framework underlying our ability to process all the relevant visual motion information, and to coordinate the appropriate motor responses. Such work is fundamental for understanding the functional organisation of the brain. It also has the potential to lay the groundwork for developments in areas of applied research, including medicine (e.g. the design of better rehabilitation strategies for people with brain damage), robotics- artificial intelligence (e.g. the improvement of artificial systems capable of vision), and the cognitive sciences (e.g. a better understanding of factors that limit human responses to visual stimuli).Read moreRead less
Therapeutic Regulation Of Matrix Metabolism To Stabilise The Biomechanical Properties Of The Sclera In High Myopia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
The Signals Of Nerve Cells That Provide The Capacity For Sight
Funder
National Health and Medical Research Council
Funding Amount
$385,115.00
Summary
Sight relies on the signals of nerve cells in the brain, but we know little about the way in which nerve cells support this, or why in some people sight is diminished. In this work we will measure the signals of nerve cells in the visual pathway to gain knowledge of these processes: we will make measurements in normal animals and in those that suffer from brain disorders. Our work will provide a scientific basis for the diagnosis and treatment of these disorders.
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less
Role Of Cortico-cortical Connections In Mediating Cerebral Cortex Plasticity: Visual Cortex Model
Funder
National Health and Medical Research Council
Funding Amount
$362,500.00
Summary
In mammals injury to the retina not only affects the neurones within the eye but also induces changes in the other parts of the brain, particularly in the visual cortex. It has been found that after retinal injury cells in the visual cortex, normally receiving an input from the injured part of the retina, now receive an input from adjacent normal retina ( ectopic receptive field ). All mammals with well developed vision have a large number of separate visual cortical areas (more than 30 in prima ....In mammals injury to the retina not only affects the neurones within the eye but also induces changes in the other parts of the brain, particularly in the visual cortex. It has been found that after retinal injury cells in the visual cortex, normally receiving an input from the injured part of the retina, now receive an input from adjacent normal retina ( ectopic receptive field ). All mammals with well developed vision have a large number of separate visual cortical areas (more than 30 in primates). These areas are arranged in a hierarchy in which it is thought that as features of the visual stimuli become more complex they are discriminated in the areas higher in the hierarchy. These higher-order areas also project back to lower-order areas. This feedback activity from the higher areas can be reversibly abolished by cooling a given area to about 10oC and then rewarming it back to its normal temperature. We will try to determine if in cats (animals with well developed vision) following damage to a small region of the retina the feedback activity from higher visual cortical areas affects the ectopic receptive fields in the lower visual cortical areas. Another possibility is that the ectopic receptive field apparent following retinal damage might depend on horizontal connections within the particular cortical area, running from normal cortex to the area of cortex affected by the lesion. We propose to test this idea by blocking reversibly (with chemical agents) transmission of these horizontal fibres and determining the characteristics of neurones in the area affected by the lesion. Understanding the role of feedback and horizontal cortico-cortical connections in establishing new ectopic receptive fields following spatially delineated damage to the retina will help us to understand the mechanisms underlying perceptual distortions and visual hallucinations which occur following retinal traumas or some age-related retinal degenerations.Read moreRead less
Neuronal Basis Of Stimulus Dependent Receptive Field Properties And The Role Of Feedback Projections
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
In mammals with a number of distinct visual cortical areas the processing of information in the visual cortex largely follows a hierarchical order. It has been widely assumed that the neurones at the highest processing level in the visual system are capable of extracting behaviorally significant features from the external visual world by virtue of their large receptive fields. However, there are massive and dense inter-connections between the cortical areas and intra-connections between the neur ....In mammals with a number of distinct visual cortical areas the processing of information in the visual cortex largely follows a hierarchical order. It has been widely assumed that the neurones at the highest processing level in the visual system are capable of extracting behaviorally significant features from the external visual world by virtue of their large receptive fields. However, there are massive and dense inter-connections between the cortical areas and intra-connections between the neurones within the same cortical area. For example the information at the higher processing levels may flow back to the lower ones via the feedback connections. Thus, it is conceivable that the neurones in the primary visual cortex (at the first stage of cortical processing) may posses the properties allowing them to integrate a considerable amount of information from a large area in visual space due to the existence of a dense web of connections. We wish to study the neuronal basis of perceptually related properties in primary visual cortex by examining the detailed receptive field properties of individual neurons and their response characteristics when more complicated visual stimuli are presented in visual space. We will also examine the influence of the feedback connections on the properties of these neurones by silencing the higher-order visual cortical areas which inversely connect to primary visual cortex. It is hoped that by relating our understanding of the basic neuronal properties to their functional roles in visual processing we will obtain further insights concerning the contributions of individual visual cortical areas (primary visual cortex in this project) to the function of visual perception.Read moreRead less