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
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.
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
Hunger flexibly modifies hypothalamic neural circuits responding to threat. Animal and human behaviour frequently involves a choice between actions or goals with conflicting positive and negative outcomes. However, the appropriate action or goal in conflicting situations often depends on physiological pressures like hunger, stress and mating opportunities. For example, the need for resources within an environment, such as food, drives approach behaviour, whereas threats to survival, such as pred ....Hunger flexibly modifies hypothalamic neural circuits responding to threat. Animal and human behaviour frequently involves a choice between actions or goals with conflicting positive and negative outcomes. However, the appropriate action or goal in conflicting situations often depends on physiological pressures like hunger, stress and mating opportunities. For example, the need for resources within an environment, such as food, drives approach behaviour, whereas threats to survival, such as predator cues, enhance avoidance behaviour. This project will uncover the neural circuitry and endocrine mechanisms through which hunger influences hypothalamic threat-detecting circuits that suppress food intake. These studies provide a new hypothalamic model to understand risk/reward decision in the brain.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