INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generat ....INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generate synchronised neuronal activity. This project aims to investigate mechanisms underlying a specific class of brain rhythm implicated in control of mood states. Positive outcomes from this basic research may lead to better drug therapies for controlling specific mental disorders.Read moreRead less
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.
Phenotyping doublecortin+ cells to unravel human adult neurogenesis. This project investigates one of the brain’s most remarkable phenomena: adult neurogenesis, the birth of new brain cells in a specialised brain area (the hippocampus) occurring well into adulthood. This process contributes to many species’ capacity to learn, remember and regenerate. However whether this process occurs in humans is heavily debated. Using new neuroscience tools, this project will produce new insights into human a ....Phenotyping doublecortin+ cells to unravel human adult neurogenesis. This project investigates one of the brain’s most remarkable phenomena: adult neurogenesis, the birth of new brain cells in a specialised brain area (the hippocampus) occurring well into adulthood. This process contributes to many species’ capacity to learn, remember and regenerate. However whether this process occurs in humans is heavily debated. Using new neuroscience tools, this project will produce new insights into human adult neurogenesis by deeply examining hippocampal cells that express the newborn cell marker, doublecortin. This will enable clarification of the existence and extent of adult neurogenesis in humans, and provide the foundation to leverage this process for improving learning, memory and brain regeneration in people.Read moreRead less
Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our underst ....Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our understanding of blood brain barrier insulin transport and dysfunction.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
The psychobiology of forgetting: Opioid receptors and inhibitory constraints on storage of long-term memory. This project has four main national benefits. First, it addresses a fundamental scientific and practical issue: the psychobiology of forgetting. Second, it will provide important insights into variations in memory functioning across the lifespan. A significant challenge facing Australia is understanding, and where possible alleviating, the decline in mental function that occurs with age. ....The psychobiology of forgetting: Opioid receptors and inhibitory constraints on storage of long-term memory. This project has four main national benefits. First, it addresses a fundamental scientific and practical issue: the psychobiology of forgetting. Second, it will provide important insights into variations in memory functioning across the lifespan. A significant challenge facing Australia is understanding, and where possible alleviating, the decline in mental function that occurs with age. This project may help identify targets to alleviate age-related impairments in memory. Third, this project will contribute to Australia's international reputation in behavioural neuroscience. Fourth, this project will provide outstanding training opportunities for Australian undergraduate and postgraduate research students in behavioural neuroscience.Read moreRead less
Models of adolescent drug use and its consequences. Recent concerns surround the impact of drug abuse - particularly binge drinking, inhalant abuse and cannabis use - on the mental health of adolescents. Early drug use is associated with mental health problems although the mechanisms involved are not well characterised. The present proposal aims to use animal models to characterise substance abuse that occurs during the adolescent period and to investigate its effects on brain and behaviour. Inc ....Models of adolescent drug use and its consequences. Recent concerns surround the impact of drug abuse - particularly binge drinking, inhalant abuse and cannabis use - on the mental health of adolescents. Early drug use is associated with mental health problems although the mechanisms involved are not well characterised. The present proposal aims to use animal models to characterise substance abuse that occurs during the adolescent period and to investigate its effects on brain and behaviour. Increasing our knowledge of the causes and consequences of adolescent drug abuse will improve Australia's ability to confront this problem and to develop early interventions and treatments that minimise associated harms.Read moreRead less
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
Functional imaging of colour pathways in the living eye. In order to repair or regenerate a diseased eye, we require knowledge of the normal pattern or nerve cell connections, and knowing how biology solves the problem of colour vision can be used to improve the design of artificial vision systems. The adaptive optics machine we will build in this project can be used to image nerve cells, fine blood vessels, and nerve fibre bundles in the normal and diseased eye. This will improve Australia's re ....Functional imaging of colour pathways in the living eye. In order to repair or regenerate a diseased eye, we require knowledge of the normal pattern or nerve cell connections, and knowing how biology solves the problem of colour vision can be used to improve the design of artificial vision systems. The adaptive optics machine we will build in this project can be used to image nerve cells, fine blood vessels, and nerve fibre bundles in the normal and diseased eye. This will improve Australia's research and development capacity in this new area of medical diagnostics. Our machine will be made available to other Australian laboratories and will improve the national capacity for making further scientific discoveries about how the visual system works.Read moreRead less