Humans, like all animals, receive similar, although not identical, visual input via the eyes. This information is combined in the brain to form a single view of the outside world. In this proposal we aim to understand how single neurons in the brain process the combined information received from both eyes. This work will increase our understanding of the underlying cellular mechanisms responsible for sight, and determine what changes occur when visual input is impaired through blindness.
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less
Thalamic inputs and cortical microcircuitry underlying the functional architecture of the visual cortex. This project seeks to reveal the fundamental circuitry of the visual cortex that enables visual perception. Such understanding is essential not only for explaining many perceptual disturbances, but also for providing a neuronal basis for developing functionally useful prostheses for the blind.
Histamine and non-visual regulation of retinal signalling. This project is internationally competitive, asking basic biological questions about the brain and vision. Of direct national benefit, the new knowledge generated may alter the way we understand how vision works. Ultimately this knowledge may give insight into particular health issues, such as the persistence of visual memory in Post Traumatic Stress Disorder, and age related diseases such as Alzheimer's disease. Further this new kno ....Histamine and non-visual regulation of retinal signalling. This project is internationally competitive, asking basic biological questions about the brain and vision. Of direct national benefit, the new knowledge generated may alter the way we understand how vision works. Ultimately this knowledge may give insight into particular health issues, such as the persistence of visual memory in Post Traumatic Stress Disorder, and age related diseases such as Alzheimer's disease. Further this new knowledge will flow directly into the reputation of our major institutes of higher education and strengthen their place on the world stage. Through both CIs, this research will contribute to the education of both undergraduate and postgraduate science students at The University of Melbourne. Read moreRead less
Functional pathways in primate retina. When light enters the eye, specialised nerve cells called photoreceptors transform the light signal into nerve signals. These signals are processed in the retina by two groups of neurones, bipolar and ganglion cells before being sent to higher brain centres. Bipolar and ganglion cells can be subdivided into several types. We will measure which types communicate with each other and which proteins (neurotransmitter receptors) are involved at the site of commu ....Functional pathways in primate retina. When light enters the eye, specialised nerve cells called photoreceptors transform the light signal into nerve signals. These signals are processed in the retina by two groups of neurones, bipolar and ganglion cells before being sent to higher brain centres. Bipolar and ganglion cells can be subdivided into several types. We will measure which types communicate with each other and which proteins (neurotransmitter receptors) are involved at the site of communication between these nerve cells. This study will improve our knowledge of the basis of functional subspecialisation at the earliest stages of the visual process.Read moreRead less
Listen and learn - statistical learning and the adapting auditory brain. This project aims to explore the link between rapid neural adaptation - a form of learning referred to as statistical learning - and human listening performance in noisy environments. The project aims to generate a new understanding of mechanisms that contribute to listeners' abilities to understand speech in noise, and to complex communication disorders such as dyslexia. Expected outcomes will include increased capacity to ....Listen and learn - statistical learning and the adapting auditory brain. This project aims to explore the link between rapid neural adaptation - a form of learning referred to as statistical learning - and human listening performance in noisy environments. The project aims to generate a new understanding of mechanisms that contribute to listeners' abilities to understand speech in noise, and to complex communication disorders such as dyslexia. Expected outcomes will include increased capacity to investigate a broad range of cognitive and communication functions. Benefits will include potential technologies and algorithms to assist listening (in devices such as hearing aids), language development and reading.Read moreRead less
Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will ....Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will be related to the properties of neurones in those areas and to those of individual input and output fibres. An optical imaging equipment will be acquired in 2004 using a recently awarded LIEF grant to the CI.Read moreRead less
Synaptic and network properties underlying neural coding in the mammalian visual cortex. This study will:
(1) Increase our basic understanding of visual function that can help to explain many clinical perceptual disturbances. (2) Help in providing a detailed picture of intracortical neuronal networks that can form the basis for a prosthesis for the blind. (3) Discover the principles of neural organization underlying functions such as figure-ground segregation and perceptual learning which can i ....Synaptic and network properties underlying neural coding in the mammalian visual cortex. This study will:
(1) Increase our basic understanding of visual function that can help to explain many clinical perceptual disturbances. (2) Help in providing a detailed picture of intracortical neuronal networks that can form the basis for a prosthesis for the blind. (3) Discover the principles of neural organization underlying functions such as figure-ground segregation and perceptual learning which can inspire practical algorithms for robotic vision. (4) Train graduate students and postdoctoral fellows in state of the art techniques in a stimulating intellectual environment.Read moreRead less
Thalamo-cortical organisation in visual information processing. This study will: (1) Increase our basic understanding of visual function that can help to explain many clinical perceptual disturbances. (2) Help in providing a detailed picture of intracortical neuronal networks that can form the basis for a prosthesis for the blind. (3) Discover the principles of neural organization underlying functions such as figure-ground segregation and perceptual learning which can inspire practical algorithm ....Thalamo-cortical organisation in visual information processing. This study will: (1) Increase our basic understanding of visual function that can help to explain many clinical perceptual disturbances. (2) Help in providing a detailed picture of intracortical neuronal networks that can form the basis for a prosthesis for the blind. (3) Discover the principles of neural organization underlying functions such as figure-ground segregation and perceptual learning which can inspire practical algorithms for robotic vision. (4) Train graduate students and postdoctoral fellows in state of the art techniques in a stimulating intellectual environmentRead moreRead less
Organisation of the cerebral cortex- what, if anything, is a cortical area? Currently, much effort is being directed towards elucidating the roles of different regions of the cerebral cortex. "Maps" of cortical areas have become essential points of reference, exerting a powerful influence on the way we think about the brain. However, is it really appropriate to model the cortex as a mosaic of well-defined areas? This project will challenge the assumptions underlying current brain mapping efforts ....Organisation of the cerebral cortex- what, if anything, is a cortical area? Currently, much effort is being directed towards elucidating the roles of different regions of the cerebral cortex. "Maps" of cortical areas have become essential points of reference, exerting a powerful influence on the way we think about the brain. However, is it really appropriate to model the cortex as a mosaic of well-defined areas? This project will challenge the assumptions underlying current brain mapping efforts. Its main benefits will be the refinement of strategies for brain mapping, including potential for better
application/interpretation of available medical technology, and unique insights on the mechanisms of development and evolution of the nervous system.
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