Targeting Of Callosal Axons To Duplicate Cortical Areas In The Contralateral Hemisphere
Funder
National Health and Medical Research Council
Funding Amount
$600,785.00
Summary
The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain ....The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain is wired in order to function correctly.Read moreRead less
Guidance Mechanisms Regulating The Development Of Axonal Projections From The Cingulate Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$484,236.00
Summary
The corpus callosum is the largest fibre tract in the brain and connects neurons in the left and right cerebral hemispheres. A subpopulation of callosal axons arise from neurons in the cingulate cortex and are the first to cross the midline. Defects in activation or wiring of the cingulate cortex are strongly implicated in acute pain, schizophrenia and bipolar disorder. This proposal investigates how the commissural projections of the cingulate cortex become wired up during development.
Cellular And Molecular Regulation Of Interhemispheric Fusion
Funder
National Health and Medical Research Council
Funding Amount
$449,489.00
Summary
In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the ....In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the interhemispheric fissure to mediate fusion.Read moreRead less
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less
Neurodevelopmental Mechanisms And Early Intervention In Psychiatric Illness
Funder
National Health and Medical Research Council
Funding Amount
$652,765.00
Summary
Schizophrenia and depression are devastating mental illnesses and a huge burden to society. Drug treatments can be beneficial, but many patients are either treatment-resistant or show severe side-effects. There is an urgent need for truly novel treatment strategies which should ideally prevent symptoms. The main aim of this project is to elucidate brain mechanisms involved in schizophrenia and depression development to inform clinical research about improved preventative treatment strategies.
Sez-6 Signalling Mechanisms And Function In The Developing Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$501,815.00
Summary
Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the or ....Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the organization of the cortex (thickness, layer patterning and regional specialization) is very similar in these two organisms, and indeed, in all mammals. A complex series of developmental events is required to produce a normal brain cortex. Malformations in the cortex occurring in human neurological disorders, including epilepsy and mental retardation, result from mutations in genes regulating crucial developmental processes. Failure of developing nerve cells to make the correct connections can result in these, or other, debilitating neurological conditions. We have evidence that a brain protein called Seizure-related gene 6 (Sez-6) regulates normal connectivity and function of neurons in the mature cortex. We will determine the molecular pathways used for signalling of Sez-6 and also investigate in detail the formation of connections between cortical neurons early in development and how these connections become aberrant in the absence of Sez-6 function.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101311
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Role of intrinsic versus extrinsic cues in cell type determination during development and regeneration. During development all of the different cell types are generated by the action of genes and also signals from the embryo that read out which cell types are present or missing. This project studies how much environmental signals affect cell type generation developmentally and if they can be used to regenerate only the types missing in different diseases.
Genetic Cues Responsible For Interneuron Migration And Layering In The Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$650,250.00
Summary
Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in ....Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in sufficient numbers, or impediments to neuron migration to proper destinations are certain recipes for neurological disorders, including epilepsy and mental retardation. In this application, we will study how neurons are assembled in the cortex. We will focus on a subpopulation known as interneurons that are vital for toning down electrical discharges from excitatory neurons. We will investigate how these neurons are able to migrate long distances to settle into defined layers of the cortex. Mutant mice with deleted genes have a defect in this process and the aim of this project will be to study the precise mode of action for some of these genes.Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
The role of preferred brain states in perceptual and cognitive processing: New insights into brain dynamics. New insights into brain dynamics will improve our understanding of both normal and atypical functioning. Extending previous work on normals will confirm how innovative Australian approaches can lead the research agenda in basic neuroscience, at the psychology-physiology interface. Testing in AD/HD and elderly populations will clarify dysfunctional brain mechanisms underlying AD/HD, and th ....The role of preferred brain states in perceptual and cognitive processing: New insights into brain dynamics. New insights into brain dynamics will improve our understanding of both normal and atypical functioning. Extending previous work on normals will confirm how innovative Australian approaches can lead the research agenda in basic neuroscience, at the psychology-physiology interface. Testing in AD/HD and elderly populations will clarify dysfunctional brain mechanisms underlying AD/HD, and the cognitive losses in elderly populations (exacerbated by dementia). These results may lead to better diagnosis, treatment, and community understanding of these groups. Also, publications on these target groups will demonstrate internationally the widespread utility of this approach, encouraging further novel applications of basic neuroscience in health.Read moreRead less