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.
Strategies To Restore Bladder Control After Peripheral Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$519,967.00
Summary
A major complication of pelvic surgery is loss of bladder control, mainly due to nerve injury at the time of removing cancerous tissue. This has a big effect on quality of life. Very little research has been conducted on injured bladder nerves. In this project we will investigate what happens to bladder nerves after injury and how we can make them regrow. We will also investigate if undamaged bladder nerves can be made to compensate for the lost function.
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.
Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
The Role Of The Orbitofrontal Cortex In Disorders Of Response Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$515,488.00
Summary
We will investigate the role of the orbitofrontal cortex (OFC) in decision-making, particularly the effect of hyperactivity in the medial vs. ventrolateral orbitofrontal cortex on decision-making. Hyperactivity in these structures has been linked to obsessive compulsive disorder and, in line with the distinct functions of the different regions of OFC, we develop and test a novel hypothesis as to the psychological and neural bases of the obsessions and compulsions distinctive to that disorder.
CCR4/NOT Complex Is A Conserved Regulator Of Heart Function
Funder
National Health and Medical Research Council
Funding Amount
$467,567.00
Summary
Cardiovascular diseases kill an Australian every 11 minutes. The goal of this proposal is to characterize the role of the conserved heart regulators in cardiac function and disease. Our combined multi-species and informatics approach has identified a major disease locus for sudden cardiac death in humans, which we propose to characterize. This work can lead to new classes of drugs to improve cardiac health and also aid in early diagnosis of patients susceptible to sudden cardiac death.
The Role Of Sodium Channels In Pain And Cold Allodynia
Funder
National Health and Medical Research Council
Funding Amount
$349,306.00
Summary
Many types of chronic pain remain poorly treated and severely impact the quality of life of millions of Australians. Cold allodynia in particular, which occurs in several painful human conditions and leads to severe pain from simply touching a cool surface or item, is poorly understood and thus difficult to treat. The aim of this project is to determine the pharmacological mechanism of cold allodynia to develop novel treatment approaches.
Targeting Lipids Regulated In A Setting Of Physiological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$489,970.00
Summary
Existing heart failure therapies largely delay heart failure progression rather than reversing the disease. New therapeutic strategies with the ability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether lipids that are secreted by the heart in a setting of “good” physiological heart growth (as occurs with exercise) can be targeted to restore function of the failing heart.