Molecular Determinants Of Inhibitory Synaptic Function Studied Using Mutant And Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, ....Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, our aim is to use a range of naturally occuring mice mutants, as well as transgenic mice to modulate the receptor levels and so to examine the role of synaptic function and synaptic dynamics. The outcomes of this project will provide fundamental new knnowledge aimed at understanding how communication in the nervous system works and may suggest ways in which modulation of this information flow could be used to treat disorders of brain function.Read moreRead less
Mechanism Of Signal Transduction And Receptor Activation In Ligand Gated Ion Channel Receptors
Funder
National Health and Medical Research Council
Funding Amount
$456,000.00
Summary
This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. It will use a range of molecular advances made by this and other laboratories to clarify how neurotransmitters enable their receptors to activate and signal. This fundamental information is of major medical significance as defective synaptic transmission, caused by mutations in ligand gated ion channel receptors, give rise to a num ....This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. It will use a range of molecular advances made by this and other laboratories to clarify how neurotransmitters enable their receptors to activate and signal. This fundamental information is of major medical significance as defective synaptic transmission, caused by mutations in ligand gated ion channel receptors, give rise to a number of neurological and psychiatric disease states. The ligand gated receptors are also major targets for therapeutic drugs and the information gained in this study may also provide insights into new ways in which drugs could be used to enhance or inhibit synaptic signalling.Read moreRead less
Receptor Signalling Through Intracellular Calcium Stores In Chromaffin Cells
Funder
National Health and Medical Research Council
Funding Amount
$461,000.00
Summary
The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modi ....The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modified by hormones and transmitters and in how these complex calcium signals are used by cells to control their function. This project will investigate how hormones and transmitters can produce different types of calcium signals in nerve cells, and how these signals affect different aspects of the nerve cell's function. In particular, it will establish how two different types of specialised calcium stores within nerve cells are used by different classes of hormone and transmitter, and the distinct cellular functions these two calcium stores can regulate. The results will provide fundamental new information on how nerve cells control their activity and may help identify potential new targets for drugs.Read moreRead less
Factors Affecting The Conductance Of GABA(A) Channels
Funder
National Health and Medical Research Council
Funding Amount
$406,650.00
Summary
GABA(A) receptors provide most of the inhibition in the brain. If they are blocked, animals suffer from seizures and die. They are the target for a wide variety of medically useful drugs such as anaesthetics, tranquillisers such as valium and anti-epleptic drugs. All these drugs boost their effectiveness and increase inhibition in the brain. Most of them were discovered by chance. In this project, we will find out more about these receptors. This will give us more information about how the brain ....GABA(A) receptors provide most of the inhibition in the brain. If they are blocked, animals suffer from seizures and die. They are the target for a wide variety of medically useful drugs such as anaesthetics, tranquillisers such as valium and anti-epleptic drugs. All these drugs boost their effectiveness and increase inhibition in the brain. Most of them were discovered by chance. In this project, we will find out more about these receptors. This will give us more information about how the brain works and also help in the search for better, more selective drugs.Read moreRead less
The Role Of Neuronal Hyper-excitability In An Animal Model Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$558,170.00
Summary
Every day at least one person in Australia dies of the fatal and untreatable adult neurodegenerative disease of amyotrophic lateral sclerosis (motor neuron disease). This research examines the factors driving early increases in neural activity which may lead to the loss of upper and lower motor neurons in adulthood. The use of new methods to suppress production of specific proteins causing increased neural activity may lead to novel treatments for this disease.
Identification And Function Of Kv7-M-channels In Axons Of Cortical Neurons
Funder
National Health and Medical Research Council
Funding Amount
$324,930.00
Summary
Membrane proteins permeable to potassium ions provide an important break during hyperexcitability of nerve cells in the brain. In this proposal I will study the function of a unique member of potassium channel protein (the M-channel) located at key regions of nerve cells; the axon. The results will provide important insights into the elementary steps of nerve cell excitability, and a better understanding of M-channel related diseases including neonatal epilepsies and chronic nerve pain.
Mechanisms Underlying Short- And Long-term Plasticity At The Mossy Fibre -> CA3 Synapse In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$272,750.00
Summary
Synapses, the contacts between brain cells, are extremely plastic. They can become stronger and weaker depending on the activity they experience. The hippocampus, a structure in the brain, is known to be critical to the formation of conscious memories. The plastic nature of the synapse in this structure is thought to underlie learning and memory. Understanding the mechanisms that are responsible for the changes in synaptic strength in the hippocampus are therefore important to our understanding ....Synapses, the contacts between brain cells, are extremely plastic. They can become stronger and weaker depending on the activity they experience. The hippocampus, a structure in the brain, is known to be critical to the formation of conscious memories. The plastic nature of the synapse in this structure is thought to underlie learning and memory. Understanding the mechanisms that are responsible for the changes in synaptic strength in the hippocampus are therefore important to our understanding of learning and memory. This proposal describes a series of experiments that are designed to determine the mechanisms of plastic changes . We hope, that by understanding these mechanisms, we can start to understand how we learn and remember.Read moreRead less
PROBABILITY OF QUANTAL SECRETION AT NEUROMUSCULAR SYNAPSES
Funder
National Health and Medical Research Council
Funding Amount
$334,232.00
Summary
The classical preparation for the study of synaptic transmission is the amphibian neuromuscular junction, for which there is the largest body of experimental data. This synapse was instrumental in the discovery that transmitters are released in packets or quanta, that this occurs at specialized release sites in the nerve terminal, and that receptor molecules on the muscles cells are strategically placed to receive the transmitter. Our work on this synapse has shown that each of these release sit ....The classical preparation for the study of synaptic transmission is the amphibian neuromuscular junction, for which there is the largest body of experimental data. This synapse was instrumental in the discovery that transmitters are released in packets or quanta, that this occurs at specialized release sites in the nerve terminal, and that receptor molecules on the muscles cells are strategically placed to receive the transmitter. Our work on this synapse has shown that each of these release sites have different probabilities for the secretion of a quantum and that this probability is correlated with the width of the release site. More recently we have shown that, whilst the size of a quantum does not vary between adjacent release sites, the area over which the quantum is released does vary between sites. The probability of quantal secretion is proportional to this area, as is the number of vesicles present at the release site. In this project we intend to relate this probability of secretion to the proteins that regulate the release of a quantum and in particular how these proteins interact to determine the time course of increase in probability at a release site after the passage of an impulse. The affects of trains of impulses on this probability are also to be delineated, in particular how the calcium which enters the terminal during these trains determines a long-term enhancement in probability after the train has ceased. This research will provide a molecular description of secretion from motor-nerve terminals.Read moreRead less
Modulation Of Calcium Signalling By Acetylcholine In The Basolateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$266,748.00
Summary
The amygdala is an area of the brain involved in assigning emotional significance to sensory stimuli. This grant examines the cellular processes involved in making these associations. Specifically, it studies the relationship between two signalling molecules implicated in association learning, acetylcholine and calcium. This research will test hypotheses of memory formation and provide insight into disorders linked to detrimental emotional associations, such as anxiety and addiction.