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
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
A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quanti ....A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quantitative model of the basic processes underlying this imaging will enable precise interpretation of such brain scans and increase their usefulness both as a research and as a therapeutic tool.Read moreRead less
Sensory Coding Mechanisms in Rat Somatosensory System; A Combined Behavioural and Electrophysiological Approach. This inter-disciplinary project spans behavioural sciences, neurophysiology and computational neuroscience. It investigates fundamental questions such as how different aspects of stimuli are presented in sensory areas of the brain and how the animal interprets the neuronal activity in such areas to generate the relevant behaviour. A major problem with making prosthetic sensory devices ....Sensory Coding Mechanisms in Rat Somatosensory System; A Combined Behavioural and Electrophysiological Approach. This inter-disciplinary project spans behavioural sciences, neurophysiology and computational neuroscience. It investigates fundamental questions such as how different aspects of stimuli are presented in sensory areas of the brain and how the animal interprets the neuronal activity in such areas to generate the relevant behaviour. A major problem with making prosthetic sensory devices is the way by which these devices can communicate with the brain. Research into the coding of different features of simple stimuli will provide basic knowledge which can be implemented in prosthetic sensory devices. Read moreRead less
Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. Read moreRead less
Brain lateralization: its function, evolution, development and change with ageing. Brain research is undoubtedly one of the key research fields today. This project involves highly innovative research at the highest international level, keeping Australia at the forefront of research on brain lateralization, a very important field of brain research in humans and animals (co-founded by the applicant). This project 1) investigates dynamic changes of the developing, mature and ageing brain for vital ....Brain lateralization: its function, evolution, development and change with ageing. Brain research is undoubtedly one of the key research fields today. This project involves highly innovative research at the highest international level, keeping Australia at the forefront of research on brain lateralization, a very important field of brain research in humans and animals (co-founded by the applicant). This project 1) investigates dynamic changes of the developing, mature and ageing brain for vital functions using animal models, thus contributing importantly to our understanding of normal functions of the human brain, including some forms of mental dysfunction and also ageing; 2) trains postgraduate students at the highest standards and 3) maintains important collaboration with colleagues in Europe. Read moreRead less
Redefining the metallothionein's role in the injured brain: extracellular metallothioneins play an important role in astrocyte-neuron responses to injury. This project is being performed by an Australian team of researchers who are leaders in this field of research, and has significant national benefits in supporting this team reveal fundamental information on the cellular interactions that occur between astrocytes and neurons within the injured brain. In national terms, it will contribute to th ....Redefining the metallothionein's role in the injured brain: extracellular metallothioneins play an important role in astrocyte-neuron responses to injury. This project is being performed by an Australian team of researchers who are leaders in this field of research, and has significant national benefits in supporting this team reveal fundamental information on the cellular interactions that occur between astrocytes and neurons within the injured brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or neurodegenerative disease. Furthermore, this research contributes directly to the Designated National Research Priorities by identifying some of the earliest biochemical and cellular processes associated with aging or disease of the brain.Read moreRead less
Are there advantages in having a lateralized brain? Specialisation of the left and right hemispheres of the brain to process different information and to control different responses is not, as once thought, unique to humans but common to all vertebrates. In fact, the same general pattern of lateralization occurs in amphibians, reptiles, birds and mammals. Until now, it has been important to document the presence and nature of lateralization in different species. Now it is important to discover t ....Are there advantages in having a lateralized brain? Specialisation of the left and right hemispheres of the brain to process different information and to control different responses is not, as once thought, unique to humans but common to all vertebrates. In fact, the same general pattern of lateralization occurs in amphibians, reptiles, birds and mammals. Until now, it has been important to document the presence and nature of lateralization in different species. Now it is important to discover the advantages (and disadvantages) of having a lateralized brain. This project will do so using two model species, the chick and the marmoset, and new techniques to measure behaviour.Read moreRead less