How do interactions between axon guidance molecules bring about directed axon growth? This project deals with a fundamental, yet poorly understood biological problem at the cutting edge of international science - how axons navigate to their targets. A better understanding of this basic biological process will greatly assist the development of therapies to treat a wide range of clinical conditions in which axonal connections between neurons are disrupted by trauma or disease.
Development of sympathetic nerve pathways. The mature nervous system contains many types of neurons connected in precise ways. Developing neurons must make many decisions about what type of neuron to become and what connections to make. This study looks at the mechanisms that guide the developing neurons in these important decisions.
Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that ....Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that this region has multiple subdivisions, but how exactly these interact in allowing the sensory information to guide arm and hand muscles is unknown. Discovering how this happens in terms of cellular interaction can have profound implications for the creation of new technologies such as artificial limbs and autonomous robots, and result in health benefits.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.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
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
Complexity in a mesoscopic model of brain dynamics. Research into how the brain work remains at the frontier of human knowledge. We possess only the vaguest idea how the brain is able to generate memories, perceptions and behaviour. This research proposal concerns new approaches aimed at bridging this gap in our understanding by developing and studying detailed theories of the brain's electrical activity. The outcomes of this work will not only suggest improved diagnostic methods and treatments ....Complexity in a mesoscopic model of brain dynamics. Research into how the brain work remains at the frontier of human knowledge. We possess only the vaguest idea how the brain is able to generate memories, perceptions and behaviour. This research proposal concerns new approaches aimed at bridging this gap in our understanding by developing and studying detailed theories of the brain's electrical activity. The outcomes of this work will not only suggest improved diagnostic methods and treatments but contribute vital knowledge about how to control and predict the behaviour of complex systems.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
Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers ....Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers G protein-coupling to the intracellular portion of the GABA-BR2 subunit. Focus will be on different modes of GPCR signalling, including constitutive activity and roles for membrane and cytosolic regulatory proteins. Targeted studies of GABAB receptor subunits will provide new information on the mechanistic regulation of GPCR signalling.Read moreRead less