Experimental Validation Of A Clinical Indicator Of Utricular Function.
Funder
National Health and Medical Research Council
Funding Amount
$198,689.00
Summary
The vestibular system is responsible for our sense of balance, it is located in the inner ear and is responsible for maintaining posture and helping an organism to make appropriate eye movements when the head moves. Damage to the vestibular system by disease or accident is extremely debilitating for a patient. A chief goal of our research program is to develop simple tests of the vestibular system that can be used in the clinic to diagnose vestibular disorders. Most present clinical tests only t ....The vestibular system is responsible for our sense of balance, it is located in the inner ear and is responsible for maintaining posture and helping an organism to make appropriate eye movements when the head moves. Damage to the vestibular system by disease or accident is extremely debilitating for a patient. A chief goal of our research program is to develop simple tests of the vestibular system that can be used in the clinic to diagnose vestibular disorders. Most present clinical tests only test the part of the vestibular system that responds to angular rotations (the semicircular canals). There are few good tests that can reliably diagnose problems concerned with sensed position (the otoliths). Recent evidence from human studies has shown that by delivering small electrical currents (galvanic stimulation) via electrodes located on the surface of the skin behind the ears, a characteristic pattern of eye movement occurs. Our hypothesis is that the distinctive pattern of eye movement produced is a result of otolith stimulation. The aim of this project is to determine exactly how these small currents produce the eye movements and if these eye movements are in fact mediated by the otoliths. To determine the physiology that underlies these types of responses we are unable to conduct these experiments in humans. Our present program will therefore use both behavioural and physiological experiments on guinea pigs to test our hypotheses about galvanic stimulation and otolith function. The significance of this work lies in that it will lead to a new way of evaluating the function of the gravity sensing part of the human vestibular system which appear to be uniquely important for patients with balance problems.Read moreRead less
The Significance Of Glial Dysfunction In Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will determine whether substances released from dying photoreceptors cause the death of neighbouring cells. In addition we will examine whether treatments that block the actions of these released substances can prevent the death of photoreceptors, thereby providing a novel therapeutic agent for the treatment of devastating eye diseases.
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.
Cochlear Mechanisms Of Otoacoustic Emission Generation
Funder
National Health and Medical Research Council
Funding Amount
$311,989.00
Summary
Deafness, both congenital and acquired, is likely to be one of the major causes of disability in the Australian workforce, in young Australians, and in some categories of pre-term infants in the next decade or two. While not life-threatening, hearing impairment deprives individuals of one of their most basic social needs: the ability to communicate with others. Although little can be done to recover lost hearing, it is important to detect hearing loss as early as possible in order to reduce furt ....Deafness, both congenital and acquired, is likely to be one of the major causes of disability in the Australian workforce, in young Australians, and in some categories of pre-term infants in the next decade or two. While not life-threatening, hearing impairment deprives individuals of one of their most basic social needs: the ability to communicate with others. Although little can be done to recover lost hearing, it is important to detect hearing loss as early as possible in order to reduce further loss (by behaviour modification in the case of noise-exposed adults) and to provide hearing assistance in very young children so that they may be exposed to some degree of auditory experience at as early an age as possible. To this end, the phenomenon of otoacoustic emissions, or noises from the ear, now recognised for twenty years, is likely to become even more significant in the early years of the next millennium. Otoacoustic emissions were first demonstrated as very soft echoes re-emerging from the ear after a delay of ten milliseconds or so following a click stimulus. These echoes are sounds produced by the ear as it goes about its normal function and are lost if the hearing sensitivity of the individual is below normal. Several other forms of otoacoustic emissions have been discovered and rapidly applied to the testing of hearing so that today the technique of assessing hearing status in neonates and others unable to co-operate, as well as in diagnostic applications, is widespread. The application of the technique, however, has preceded a real understanding of what otoacoustic emissions are and how they are generated, and their widespread use at the moment is somewhat akin to a car repair industry which does not understand how an engine works. This proposal intends to investigate the basic mechanisms behind otoacoustic emissions in order to improve their efficiency and accuracy of clinical interpretation.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.
Cortical Interactions Between Afferent Channels In Macaque Visual System
Funder
National Health and Medical Research Council
Funding Amount
$380,154.00
Summary
There are three distinct groups of cells that carry the visual information from the eyes to the brain, each pathway signaling a different aspect of the visual scene. This project will study in detail the lesser known of these three pathways (koniocellular neurones): what sort of information they carry into the brain, how it is combined with the other pathways to yield our composite picture and where in the brain such combination takes place.
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
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
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
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