Assembly of neural circuits during development. This program aims to understand how nerve cells wire up accurately during development. Specifically, the program will determine how neuronal connections are established in the retina to produce a sensory structure essential for vision. The program will also generate innovative tools for watching in live animals, the making and breaking of connections during normal and abnormal development. Discoveries will not only significantly increase our knowle ....Assembly of neural circuits during development. This program aims to understand how nerve cells wire up accurately during development. Specifically, the program will determine how neuronal connections are established in the retina to produce a sensory structure essential for vision. The program will also generate innovative tools for watching in live animals, the making and breaking of connections during normal and abnormal development. Discoveries will not only significantly increase our knowledge base of how the nervous system develops or degenerates, but the results will provide crucial information for future studies based on genetic approaches, drug therapies and bioengineering technology to repair the injured nervous system.Read moreRead less
Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of ....Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of this work is to provide basic knowledge about the processes that underlie correct brain formation and function, and to understand what processes are disrupted when the brain fails to function correctly. Such disruptions lead to mental retardation and learning difficulties, and in the aged, an inability to form and store new memories, as occurs in dementia.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
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.Read moreRead less
Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System ....Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System. GLTx provide a new tool to further dissect the role of Cav2.2 in controlling neurotransmitter release. GLTx also greatly facilitates synaptic vesicle recycling, suggesting an unexpected link between Cav2.2 activation and the compensatory endocytic machinery. Our goal is to investigate functional coupling between Cav2.2 and the exo- and endocytic machineries using GLTx.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Mechanisms of fear learning and extinction in the mammalian brain. The brain is a remarkable machine that coordinates all aspects of our daily lives including the storage and retrieval of memories. Given that many age-related degenerative disorders are associated with marked changes in learning and memory it also has implications for Australia's National Research Priority 2 "Ageing well and ageing productively". This research aims to discover the basic mechanisms that underlie memory storage an ....Mechanisms of fear learning and extinction in the mammalian brain. The brain is a remarkable machine that coordinates all aspects of our daily lives including the storage and retrieval of memories. Given that many age-related degenerative disorders are associated with marked changes in learning and memory it also has implications for Australia's National Research Priority 2 "Ageing well and ageing productively". This research aims to discover the basic mechanisms that underlie memory storage and how these are modulated in an emotional context. It will also shed light on states such as anxiety, depression and post-traumatic stress, enhancing our ability to identify new therapeutic targets for such disorders.Read moreRead less
A new theory for retinotectal map formation. How brains become wired up during development is a question of
importance to both biology and computing. In this project we adopt a
novel computational approach to understanding the development of
topographic maps, a wiring pattern that is ubiquitous in biological
nervous systems. This project will build capacity for research in
computational neuroscience in Australia. It may also lead to
technological benefits such as new ideas for the design o ....A new theory for retinotectal map formation. How brains become wired up during development is a question of
importance to both biology and computing. In this project we adopt a
novel computational approach to understanding the development of
topographic maps, a wiring pattern that is ubiquitous in biological
nervous systems. This project will build capacity for research in
computational neuroscience in Australia. It may also lead to
technological benefits such as new ideas for the design of self-wiring
computing devices, and new insights into
the causes of wiring defects both during normal development and
rewiring after injury.
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