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.
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.
The research outlined in this application seeks to examine the role of calcium in the pathogenesis of AD. It will examine the hypothesis that the build-up of a protein known as the Abeta causes an increase in levels of calcium in nerve cells of the brain. This increase in calcium may trigger nerve cell damage and dementia. The ultimate aim of the research is to identify new targets for drug development in Alzheimer's disease.
Elucidating The Mechanisms Of Alpha-conotoxin-induced Calcium Channel Inhibition Via G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$419,082.00
Summary
N-type voltage-gated calcium channels (VGCCs) are membrane proteins involved in neurotransmission and play a major role in pain. VGCCs are a well-established target for the development of analgesics. Our recent research identified that VGCCs can be inhibited by ?-conotoxins from the venom of marine snails by targeting ?-aminobutyric acid receptors in sensory neurons. We will characterize this novel form of modulation of VGCCs by ?-conotoxins and define the pathways that lead to VGCC inhibition.
Deciphering The Mechanisms Underlying LRP-mediated Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$370,659.00
Summary
Nerve damage can develop post injury or disease and are often very debilitating, slow to heal and cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
Do Changes In HCN Channels Function Cause Epilepsy?
Funder
National Health and Medical Research Council
Funding Amount
$386,172.00
Summary
About 100 000 people suffer from epilepsy in Australia with about one third poorly controlled with current anti-epileptic drugs. It is important to continue to develop novel modes of treatment for this debilitating disease. This project investigates an ion channel, known as HCN that is thought to be involved in making a brain epileptic. Understanding how changes in HCN channels make nerve cells and nerve networks more excitable will help us develop better strategies for designing drugs.
Targeting Early Cellular Damage During Secondary Degeneration Using Nanosphere-based Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$424,407.00
Summary
After brain injury, there are no treatments to stop the spread of damage to intact tissue, a process involving different cell types and biochemical events. Clinical trials have targeted one event and have failed because large therapeutic doses are toxic and because combined treatments are needed to target different events. We will harness nanotechnology to target delivery of small, sustained doses of one or more drugs to specific cell types and biochemical events to stop the spread of damage.
Absence epilepsy is the commonest form of idiopathic generalized epilepsy. It can lead to hundreds of seizures per day, and mainly affects children between the ages of four and eight. Its cause is in most cases unknown. In this study we will use a rat model of absence epilepsy to investigate the cellular basis of this disease. Preliminary work indicates that a particular protein - HCN1 - is reduced in the cortex of rats with absence epilepsy. This protein codes for a pore in the membrane of nerv ....Absence epilepsy is the commonest form of idiopathic generalized epilepsy. It can lead to hundreds of seizures per day, and mainly affects children between the ages of four and eight. Its cause is in most cases unknown. In this study we will use a rat model of absence epilepsy to investigate the cellular basis of this disease. Preliminary work indicates that a particular protein - HCN1 - is reduced in the cortex of rats with absence epilepsy. This protein codes for a pore in the membrane of nerve cells, which acts like a switch. We have preliminary evidence that in rats with absence epilepsy this switch does not work properly. We wish to investigate how this influences the activity of nerve cells in rats with absence epilepsy. Furthermore, as absence epilepsy is an inherited disease, we wish to track down the genetic basis of this disease. This will give us clues as to the cause of the disease in this rat model. This research will shed light on the potentially important role of the HCN1 protein in absence epilepsy, which may represent an potentially new therapeutic target for the development of drugs for the treatment of absence epilepsy.Read moreRead less
The neocortex is the region of the brain that underlies all cognitive functions. Mental disorders, such as schizophrenia, occur when the communication between nerve cells in the neocortex breaks down. We propose to make electrical measurements from the thin processes of neurons that receive input from widely separated neocortical areas to understand how areas of the neocortex are functionally interlinked, with the ultimate aim to identify how these processes are disturbed in mental disorders.