Nuclear Factor One Genes Regulate Multiple Aspects Of Cerebral Cortex Development
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
To function, the brain must be formed correctly during embryonic development. We are investigating the embryonic development of the cerebral cortex, an area involved in high-order cognitive processing. Recently, we discovered that an important group of genes regulates cortical development, making it possible to study the underlying molecular mechanisms. The results will impact the prognosis and treatment of developmental brain disorders.
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain devel ....Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain develop and become 'wired' together in the period following birth. We will also determine if there are mechanisms which allow alternate routes to be found for processing visual information while the brain is still establishing connections between its multiple areas. This will allow us to understand the anatomical and physiological bases of the deficits caused by early damage to the visual areas of the brain, and perhaps point to strategies that will lead to improved recovery of visual function.Read moreRead less
MEASURING AND MODELLING VISUAL CORTICAL PLASTICITY
Funder
National Health and Medical Research Council
Funding Amount
$612,693.00
Summary
We are the product of both our genes and our environment. Scientists have already shown that the physical structure of our brain can be changed by our experiences. But how much can it be changed? Our experiments will address this question for a particular case: how far our visual experiences can affect the structure of the part of our brain that processes visual images. This will help us understand the delicate balance between our genes and our environment in shaping who we are.
Doublecortin (Dcx): A MAP For Migration In The Developing Brain
Funder
National Health and Medical Research Council
Funding Amount
$366,100.00
Summary
When a child is born with mental retardation or epilepsy, every parent wants to know why. There are many treatable causes, including poor nutrition, damage at birth and exposure to viruses or drugs. Other triggers for mental retardation and epilepsy are neither preventable nor treatable. Of the latter group, genetic diseases are one of the most important causes and are still not fully understood. At the Children's Medical Research Institute, we are involved in finding out how the brain develops ....When a child is born with mental retardation or epilepsy, every parent wants to know why. There are many treatable causes, including poor nutrition, damage at birth and exposure to viruses or drugs. Other triggers for mental retardation and epilepsy are neither preventable nor treatable. Of the latter group, genetic diseases are one of the most important causes and are still not fully understood. At the Children's Medical Research Institute, we are involved in finding out how the brain develops normally so that we can come to understand how our genes can cause conditions such as mental retardation and epilepsy. In understanding the normal development of the brain, we have focused on a gene known as doublecortin (Dcx). Mutations in doublecortin result in both mental retardation and epilepsy in a condition known as lissencephaly (smooth brain). Children with lissencephaly have fewer nerve cells (neurons) within their brains when compared to others of the same age, a problem thought to arise before their birth. At this time, the neurons are formed deep within the brain and migrate from this starting point to a final resting place nearer to its surface. This migration fails in lissencephaly and suggests a very important role for doublecortin in normal migration and brain development. We intend to undertake biochemical approaches which will tell us Dcx function in neuronal cells and in animals which have had Dcx expression altered. Dcx is reported to interact with the cells scaffolding system (microtubules). We will investigate interactions of normal and modified Dcx with microtubules. Following on the neuronal cell studies, transgenic mice will be developed expressing normal and mutated Dcx which will allow in depth analysis of gene function in an in vivo system. Ultimately our studies will lead to an understanding of Dcx role in microtubule dynamics and its involvement in neuronal migration and lissencephaly.Read moreRead less
Plasticity Of Sensorimotor Representations In Adult Primate Cortex
Funder
National Health and Medical Research Council
Funding Amount
$554,656.00
Summary
Cells in some regions of the brain, collectively known as the sensorimotor cortex, control our capacity to purposefully move the arms and hands. Damage to these regions in adults causes severe deficits. However, rehabilitative training can restore some control over the muscles. To understand how the brain circuits change to compensate for injury, and what effect rehabilitation may have on these changes, I will study cellular alterations in the movement control pathways in the cerebral cortex.
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
Representation Of Spatial Coordinate Systems Within Posterior Parietal Cortex And Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$43,759.00
Summary
To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the ....To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the brain that perform these computations by using a relatively new technique called functional magnetic resonance imaging or fMRI. This is a non-invasive technique that requires a person to lie in an MRI scanner and perform simple eye movement tasks while the scanner takes images of the brain. With this technology we are able to determine which regions of the brain are most active during the performance of each task, thereby giving us an insight into how the brain works. An area of the brain called the parietal lobe is thought to be involved in the localization of objects, such as reaching for a cup of tea. We will study this area using fMRI to determine how a map of space is represented within the parietal lobe. This region of the brain communicates with another region, the hippocampus which is thought to be involved in navigation, such as walking about the house or driving in the city. Functional MRI will be used to study the hippocampus of our subjects while they perform simple navigational tasks through a maze which is simulated on a computer screen. This will reveal the role hippocampus plays in navigation and the relationship between the parietal lobe and hippocampus. We hope that the greater understanding of hippocampus that will arise from this study will enable us to devise a robust method for imaging hippocampal function with fMRI. We expect that these techniques will aid in the diagnosis of hippocampal abnormalities in patients with temporal lobe epilepsy.Read moreRead less
Molecular And Cellular Changes Following A Cortical Injury: What Role Do They Play In Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$499,625.00
Summary
Damage to the visual areas of the brain is common after, for example stroke, neurotrauma or hypoxia. The injury often manifests in the form of a scar caused by a specific type of brain cell (astrocyte). This scar acts as a barrier to the cells which transmit information (neurones), preventing re-establishment of connectivity, thus functional recovery. We will see if we can reduce this scar and enhance re-connectivity after injury by blocking some of the molecules that brain cells express.
Lesions of the primary visual area (V1) are sufficient to cause blindness, even though there are many other brain areas normally involved in vision. However, when V1 is lesioned very early in life people show some recovery, and may be able to see well enough to perform everyday activities. In order to understand what happens in the brain that allows this preservation of vision, we will study changes in the pathways linking the eyes to the brain, following lesions at different ages.
Bilateral Movement Therapy In Post-stroke Hemiparesis
Funder
National Health and Medical Research Council
Funding Amount
$265,993.00
Summary
Stroke is the leading cause of long-term disability in adults in Australia, accounting for approximately 25% of all disability. A common motor disability resulting from stroke is hemiparesis, weakness or paralysis on one side of the body. This disability severely impairs an individual's capacity to perform activities of daily living, making them dependent on relatives and health professionals for daily care. By developing effective interventions to treat stroke-induced hemiparesis both the disab ....Stroke is the leading cause of long-term disability in adults in Australia, accounting for approximately 25% of all disability. A common motor disability resulting from stroke is hemiparesis, weakness or paralysis on one side of the body. This disability severely impairs an individual's capacity to perform activities of daily living, making them dependent on relatives and health professionals for daily care. By developing effective interventions to treat stroke-induced hemiparesis both the disability caused by stroke and the associated personal and financial costs will be lessened. A number of interventions focusing on the affected side (unilateral), including active movements and muscle stimulation are being investigated as possible treatments for stroke-induced hemiparesis. Recent evidence suggests that involving the unaffected side simultaneously (bilateral therapies) could be effective, and may provide addtional benefits over unilateral therapies. The aim of this research is to thoroughly examine the effectiveness of bilateral therapies by incorporating them into established interventions. The findings from these studies will aid in the development and refinement of movement therapies aimed at promoting recovery from stroke-induced hemiparesis.Read moreRead less