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.
We propose to establish the Australian Mouse Brain Mapping Consortium which is a national network of facilities allowing Australian researchers to better characterise mouse models of neurological diseases such as Alzheimer's Disease and stroke. Just as accurate maps were key to the voyages of geographic discovery in the 17th and 18th century, improved methods of mapping structural and functional changes in the brain of mouse models of neurological disease will be key to discovery in the neurosci ....We propose to establish the Australian Mouse Brain Mapping Consortium which is a national network of facilities allowing Australian researchers to better characterise mouse models of neurological diseases such as Alzheimer's Disease and stroke. Just as accurate maps were key to the voyages of geographic discovery in the 17th and 18th century, improved methods of mapping structural and functional changes in the brain of mouse models of neurological disease will be key to discovery in the neurosciences in the 21st century . For the Consortium the cartographic tools will be magnetic resonance imaging (MRI), microscopy and sophisticated computational methods of mapping brain structure and function. Participants in the Consortium are internationally recognised leaders in brain imaging based at Monash University, the Howard Florey Institute, the Prince of Wales Medical Research Institute and the Centre for Magnetic Resonance and the Queensland Brain Institute, University of Queensland.Read moreRead less
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
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
Gene-environment Interactions And Synaptic Plasticity In The Developing And Dysfunctional Cerebral Cortex
Funder
National Health and Medical Research Council
Funding Amount
$526,026.00
Summary
The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of pla ....The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of plasticity in postnatal brain. Many brain disorders, including schizophrenia, autism, epilepsy, Alzheimer's and Huntington's disease, involve abnormal development or function of the cerebral cortex. Our group has recently demonstrated that onset and progression of Huntington's disease, previously considered the epitome of genetic determinism, can be modulated by environmental factors, suggesting that all brain disorders must involve gene-environment interactions. In this project we are focusing on a specific molecular pathway which processes information from the environment and induces experience-dependent changes in the structure and function of neurons in cerebral cortex. We know that the molecular pathway we are examining has been linked to schizophrenia, a disorder of brain development, and we are attempting to understand how disruption of these molecular pathways can lead to the abnormal brain development and plasticity seen in this disease. We hope to discover neurobiological mechanisms which provide integrative understanding at the level of molecules, networks of neurons, and behaviour, in mouse models of brain disorders with disruption of specific genes, receiving different types of environmental stimulation. Analysing normal mice in this project will also provide new information on mechanisms of plasticity in the healthy cerebral cortex, that may underlie higher brain functions such as learning, which occurs throughout postnatal life, and memory.Read moreRead less
Ascending Neural Networks And Behavioural State Control
Funder
National Health and Medical Research Council
Funding Amount
$727,758.00
Summary
Our research aims to describe and understand newly identified nerve pathways or 'networks' in brain that control physiological homeostasis or balance and complex behaviours, including levels of arousal and motivation, sleep/wake patterns, learning and memory, and emotions such as fear and anxiety
An Investigation Of The Potential Association Between Sports Concussion And Neurodegenerative Disease In Collision Sports Athletes
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Traumatic brain injury (TBI) is increasingly recognised as a risk factor for dementia. Sports concussion is the mildest form of TBI, but occurs frequently in contact sports, with some players sustaining multiple concussions during their career. Despite the increased attention on this topic, it is not known whether repeated concussions during an athlete’s career lead to a greater vulnerability or a greater risk for dementia later in life. This research program aims to investigate these concerns.
Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in ....Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in fear learning will enhance our ability to develop better therapeutic approaches for treating anxiety and preventing relapse, potentially through a gender-specific approach. The studies outlined in this proposal will have implications for promoting and maintaining good health.Read moreRead less
The Retina As A Chemogenetic Target For The Treatment Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Treatments for depression are often poor because they lack selectivity. By inserting receptors that respond to an inert drug, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can turn on-or-off very specific classes of cells, providing an exciting treatment direction for depression and other neuropsychiatric diseases. The long term goal of this project is to create a highly effective DREADD-based treatment for depression, which is activated by either eye drops or a pill.
Repetitive Transcranial Magnetic Stimulation Treatment Of Auditory Hallucinations In Psychotic Disorders: A Clinical And Neurobiological Investigation
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
This research will investigate a novel treatment, repetitive transcranial magnetic stimulation treatment, for auditory hallucinations of psychosis (e.g. schizophrenia). This work is novel as it will utilise an innovative and sophisticated method to optimise treatment at the individual level. Additionally, by identifying features of patients that predict response to treatment, this research will make major contributions to personalised treatment selection guidelines.