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
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine inst ....Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine instructive and multifunctional roles of peptidergic chemosensory neurons and their contribution to local inhibitory control of the respiratory network. New knowledge from the project may in the future assist translational research into respiratory disorders and lead to technological advances.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
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
Action-related learning and plasticity in the cortico-striatal network. This project focuses on the neural bases of adaptive behaviour, specifically on the neural processes through which new actions are acquired. This project aims to establish the neural networks involved as well as the locus of the critical cellular plasticity mediating this learning process in the brain.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989703
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Multiphoton microscope for cellular imaging in live animals. The proposed facility will for the first time allow scientists across Sydney to monitor cell function in intact brain and muscle tissues. The novel optical approach combines fluorescent markers with sophisticated microscopy. The presence of this facility will allow Australian scientists to design new approaches to fundamental biological questions concerning cellular function within the normal environment. In addition this facility wi ....Multiphoton microscope for cellular imaging in live animals. The proposed facility will for the first time allow scientists across Sydney to monitor cell function in intact brain and muscle tissues. The novel optical approach combines fluorescent markers with sophisticated microscopy. The presence of this facility will allow Australian scientists to design new approaches to fundamental biological questions concerning cellular function within the normal environment. In addition this facility will allow PhD and post-doctoral scientists to train and have access to a rapidly developing and cutting edge approach to biological problems.Read moreRead less
Optimizing autonomous system control with brain-like hierarchical control systems. Autonomous robotic systems, those requiring minimal ongoing supervision, have enormous commercial, medical and industry potential. A robotic hand, permitting manipulation of material objects is an integral part of robot function. Many aspects of human hand control, such as learning, fine motor control, context-specific adaptation and recovery from system damage would be greatly beneficial to a robotic hand. Likewi ....Optimizing autonomous system control with brain-like hierarchical control systems. Autonomous robotic systems, those requiring minimal ongoing supervision, have enormous commercial, medical and industry potential. A robotic hand, permitting manipulation of material objects is an integral part of robot function. Many aspects of human hand control, such as learning, fine motor control, context-specific adaptation and recovery from system damage would be greatly beneficial to a robotic hand. Likewise, theories of human hand control could be subject to empirical testing by implementing them in a robotic hand. These advances will greatly benefit our understanding of the human brain, with potentially wide-ranging medical benefits such as novel prosthetic limb design and rehabilitation strategies for stroke patients.Read moreRead less