Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
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
Molecular And Activity Dependent Mechanisms Regulating The Targeting Of Corpus Callosum Axons In The Contralateral Hemisphere.
Funder
National Health and Medical Research Council
Funding Amount
$413,266.00
Summary
The brain is made up of circuits of neurons that process specific information. For example, the somatosensory cortex receives and sends connections to other somatosensory areas, including the contralateral cortex, but how these systems are wired up is not known. We will investigate whether information about the size and position of the cortical areas and activity-matching of the somatosensory information received by each hemisphere are used to guide callosal axons to their targets.
Establishing A Model Of Occlusive Middle Cerebral Artery Stroke In The Sheep
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Stroke is the second leading cause of death and the highest cause of disability in adult Australians, however our lack of an animal model that correctly replicates the human condition has severely hindered our understanding and treatment of the disease. This research project aims to develop a model of stroke in the sheep using a surgical approach that future researchers may use and adapt to further explore the physiology of the disease and trial therapeutic techniques to treat stroke.
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
The mammalian cerebral cortex is an area of the brain responsible for all higher order cognitive processes. I investigate how connections from between the two cerebral hemispheres during embryonic and foetal development, thus enabling the brain to coordinate information from the two sides of the body. Malformations of these connections cause mental retardation and sensory and motor deficits. I want to understand how these brain defects occur and how best to treat them.
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
COMBIT: Randomised Controlled Trial Of Novel Upper Neurorehabilitation For Congenital Hemiplegia
Funder
National Health and Medical Research Council
Funding Amount
$486,588.00
Summary
Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of t ....Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of the intervention.Read moreRead less