Cognitive Inflexibility And The Development Of Pathological Habits In Brain Diseases
Funder
National Health and Medical Research Council
Funding Amount
$883,946.00
Summary
Pathological habits are observed in severe mental health conditions including dementia, obsessive-compulsive disorder (OCD), schizophrenia, depression and addiction. This application aims to provide the mechanistic detail required for therapeutic targeting to restore flexible decision making in these conditions.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
Targeting The Synaptic Actin Cytoskeleton In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$840,741.00
Summary
Dementias have become one of the fastest growing sources of major disease burdens in developed countries with about one in fifteen Australians older than 65 being affected. We will study how pathological stimuli disrupt nerve cell connections in the brain by impacting on the cellular architecture at these connections. Findings from our study will provide profound new insights in how nerve cells communicate with each other and how this communication is breaking down in disease.
A Potential Analgesic Target In A Novel Clinically-relevant Neuropathic Pain Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$685,811.00
Summary
Persistent pain arising from tissue damage, to nerves, muscles or joints for example, is devastating for patients and a huge social and economic burden. This work will investigate one of the pathways that goes awry after sensory nerves are damaged. These experiments will also test whether a drug being developed to treat Alzheimer's disease is effective at blocking the persistent nerve hypersensitivity that sometimes develops after injury.
Learning And Network Plasticity In A Primitive Sensory Cortex
Funder
National Health and Medical Research Council
Funding Amount
$461,557.00
Summary
Our brain is a uniquely powerful supercomputer, in part because it is ‘plastic’ -- that is, it can change itself when we adapt or learn something new. An understanding of the causes of brain plasticity is an essential part of any quest to understand the brain in sickness and in health. This research uses a laser microscope to ‘read the minds’ of mice as they learn about odours. By observing plasticity in action, we will gain deeper insights into normal brain function.
A Novel Approach For The Treatment Of Obesity: Examining The Potential Of Addiction Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$765,935.00
Summary
Difficulty in managing food intake, especially highly palatable food, can result in obesity and the health liabilities associated with being overweight. In its extreme, the difficulty reducing food intake resembles an addictive disorder. We have compelling preliminary data which show deficits in the brain associated with addiction are also found in diet-induced obesity. Therefore strategies used to treat addiction can potentially be used to treat obesity.
The Role Of Neuronal Hyperactivity And Neurotrophic Factor Signalling In Synaptogenesis, Dendrogenesis And Neuron Death In Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,331.00
Summary
Using mice with mutant genes causing amyotrophic lateral sclerosis, we will test whether motor neuron hyper-excitability during early development causes excessive synapse and dendrite formation, ultimately leading to neuronal death. We will also test whether activity-dependent secretion of neurotrophic factors and activation of their receptors plays a role in this disease. This will show whether neuronal hyper-activity and neurotrophic factor signaling plays a causal role in this disease.
Sorting Out The Synapse: The Role Of Intracellular Trafficking In NMDA Receptor Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$631,966.00
Summary
When the normal levels of cell surface proteins in neurons are reduced this can lead to a variety of debilitating neurodegenerative and neuronal diseases. These levels are maintained by organelles inside the neuron called endosomes. In this project we will examine how cell surface receptors required for synapse formation are transported through endosomes by a protein machine called retromer, which is important in both Alzheimer’s and Parkinson’s disease.
Impact Of Somatic Versus Dendritic Inhibition On Neuronal Output
Funder
National Health and Medical Research Council
Funding Amount
$1,047,686.00
Summary
The brain is made up of literally billions of neurons connected in complex networks. These neurons come in two primary flavors - excitatory and inhibitory - which work in balance. Too much excitation and the brain becomes epileptic, too much inhibitory and we go into a coma. This proposal focuses on the role of specific inhibitory cell types in regulating brain function, and has relevant to a range of neurological disorders from epilepsy, to schizophrenia to depression.
A DENDRITIC SUBSTRATE FOR THE CHOLINERGIC CONTROL OF NEOCORTICAL OUTPUT
Funder
National Health and Medical Research Council
Funding Amount
$898,340.00
Summary
The forebrain cholinergic system controls neocortical activity and cognitive function. This project will investigate the mechanisms by which the cholinergic system controls neocortical circuit activity in rodent models using advanced optical and electrical recording methods. The results will provide a foundation for the understanding of how dysfunction of the cholinergic system results in cognitive decline in humans, and identify new targets for improved treatment of human cognitive impairment.