Disorders Of Action Control And Learning-related Plasticity In The Basal Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$434,874.00
Summary
Disorders of the basal ganglia have long been known to produce severe cognitive symptoms including a deficit in the control of voluntary action. This project will assess the learning processes through which humans and other animals acquire such actions. We will systematically investigate changes in cellular plasticity associated with the acquisition of new actions to establish the role that it plays in action control under normal and pathological conditions.
Pathologies Of Action Control: Amygdala-striatal Interactions And The Development Of Habits.
Funder
National Health and Medical Research Council
Funding Amount
$431,867.00
Summary
Changes in basal ganglia function, whether produced by neurodegenerative disorders, stroke, injury or disease, can produce pathological changes in action control. This proposal will assess the role of amygdala afferents on basal ganglia structures, most notably the dorsal striatum, in this process. Using an animal model we will compare the role of central and basolateral amygdala inputs to striatum in decision-making, choice and the transition of actions to reflexive, habitual responses.
Dysfunctions In Decision-making And The Cognitive Control Of Action
Funder
National Health and Medical Research Council
Funding Amount
$647,341.00
Summary
The aim of this research project is to establish the neural bases of dysfunctions in decision-making associated with deficits in the cognitive control of action. Decision-making is a complex capacity dependent on the interaction between neural systems that mediate cognition and the selection of specific actions. To this end we will examine the intracellular, cellular and circuit level processes controlling the influence of predictive information on choice between goal-directed actions.
The aim of this research project is to provide critical new information on the functional changes in brain circuits mediating cognitive-emotional integration during decision-making. This project will use a powerful and unique combination of behavioural, circuit-level, cellular, genetic and imagining tools to assess decision processes in healthy rodent and human subjects, and in animal models of, and humans suffering from, specific psychiatric disorders.
High-resolution Brain Imaging Of Basal Ganglia Function
Funder
National Health and Medical Research Council
Funding Amount
$589,083.00
Summary
This project will develop new methods for high resolution MRI imaging of the human brain. We will assess functions of deep brain areas known as the basal ganglia that play a critical role in movement planning and co-ordination. Dysfunction within the basal ganglia is responsible for the motor impairments seen in people with Parkinson’s disease. In this project, we will examine changes in basal ganglia function and structure that lead to individual differences in movement control and learning.
Determining Neuronal Connections Involved In Parkinson's Disease And Cocaine Addiction
Funder
National Health and Medical Research Council
Funding Amount
$343,300.00
Summary
Addictive behaviours in response to cocaine use and fine motor coordination that is affected in Parkinson's disease are both controlled by the same type of cells/neurons, i.e., dopamine neurons. However, the circuitry of these neurons varies from where they originate and the type of connections they make. By understanding the neuronal circuitry of these two circuitries in concert we will be able to gain important insight into their roles in adaptive and pathological brain function.
How Does Chronic Epilepsy Result In Cardiac Electrophysiological Dysfunction?
Funder
National Health and Medical Research Council
Funding Amount
$737,112.00
Summary
Cardiac dysfunction is common in epilepsy, and could be an important contributor to the increased risk of sudden death in people with epilepsy (SUDEP). In this grant we will investigate: when changes in the cardiac function develop in relation to the epilepsy; if people with chronic epilepsy have similar changes; and what effect seizures and epilepsy has on the nerves innervating the heart. The outcomes have the potential to motivate new treatments and prevention for this important problem.
Repair Of The Nigrostriatal Pathway By Phenotype Shift Of Dopamine Neurones
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
Repairing the injured brain will depend on developing new cells that can form the correct cell type, make the right connections and be incorporated into normal brain circuitry. We have found that dopamine cells, which are lost in Parkinson's Disease, are being renewed in the adult rodent brain. This study is directed at finding factors that control this process and to exploit these factors therapeutically. We provide evidence that this can be used to treat Parkinson's Disease.
Evaluation Of Combined Mild Hypothermia And Magnesium As A Neuroprotective Therapy Following Cerebral Ischaemia/stroke
Funder
National Health and Medical Research Council
Funding Amount
$310,286.00
Summary
Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.Read moreRead less