Brain Plasticity Following Changes In Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
The research proposed here will investigate the mechanisms our brains use to adapt to changes in sensory input, as occurs following blindness, deafness, nerve damage or loss of a limb. The information gathered will help develop treatments for diseases associated with sensory loss, as well as those associated with deficits in our ability to learn and remember, such as Alzheimer's disease.
The research described in this Project Grant application should help to us understand how our brains make memories. Our brains contain billions of interconnected nerve cells forming unimaginable numbers of possible networks. Previous research indicates that repetitive activation of individual networks can lead to changes in the strength of connections between nerve cells. These changes in connection strength are thought to underlie learning and memory. The experiments described in this proposal ....The research described in this Project Grant application should help to us understand how our brains make memories. Our brains contain billions of interconnected nerve cells forming unimaginable numbers of possible networks. Previous research indicates that repetitive activation of individual networks can lead to changes in the strength of connections between nerve cells. These changes in connection strength are thought to underlie learning and memory. The experiments described in this proposal will address the mechanisms underlying changes in the strength of connections between nerve cells. As most of the inputs nerve cells receive from other nerve cells are made onto their dendrites (small branching processes that extend from the cell body), the main objective is to investigate the interactions at the dendritic level responsible for changes in connection strength. The results of this work will raise our understanding of how memories are formed, which will be essential if we are to understand the cellular processes disrupted during memory dysfunction in neurological disorders such as dementia.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.
Modulation And Trafficking Of SK Channels In The Lateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$260,980.00
Summary
The amygdala is a brain structure that underlies emotional processing. Malfunctions in emotional processing are thought to be the cause of anxiety disorders. Understanding amygdala physiology is thus vital for developing therapies to treat these disorders. We have recently found a novel role for an ion channel in controlling amygdala excitability. In this grant we will investigate how this ion channel is modulated, which will elucidate a novel way in which activity in the amygdala is regulated.
MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES
Funder
National Health and Medical Research Council
Funding Amount
$438,707.00
Summary
The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, ....The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, synaptobrevin, SNAP25 and synaptotagmin) together with a calcium channel are complexed with a docked synaptic vesicle containing a quantum of transmitter in a module of secretion appropriately called a secretosome. The leading questions here are to determine if only a single secretosome participates in transmitter release on the arrival of a nerve impulse, whether the number of these secretosomes in a varicosity determines its probability for secretion of a quantum, and fundamentally, how do the proteins within the secretosome cooperate to trigger exocytosis when there is sufficient calcium influx through the secretosome-associated calcium channel following the impulse. The other problem concerns the mechanism of removal of calcium from the varicosity once it has entered through the channels, This calcium can have considerable affects on the extent to which secretosomes participate in secretion with subsequent impulses. Furthermore, this influx of calcium can be modulated for subsequent impulses by transmitter released by the first impulse. The present research will solve these problems, providing a molecular description of secretion from single sympathetic varicosities.Read moreRead less
Identification And Origin Of Neuronal Precursors In The Adult Mouse Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$284,250.00
Summary
It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which u ....It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which ultimately results in the addition of new nerve cells that go on to repair the pathological damage. Although the production of new nerve cells under normal conditions and following damage is highly significant, we still know surprisingly little about the nature of the precursor population which produces these cells and even less about their regulation. For the most part, this has been due to our inability to identify and isolate the brain stem cell. Thus, over the last 5 years I have adapted cell sorting techniques - which are normally used to separate blood cells to isolate populations of cells from the brains of adult mice. As a result of my work, we are now in the position to sort for a population of stem cells that are known to give rise to new brain cells in the adult olfactory bulb. This work will be extended to identify and characterise the precursor population that resides in the hippocampus. The identification of this hippocampal precursor population will thus provide the foundation for developing new approaches for the treatment of diseases such as strokeRead moreRead less
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
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
Molecular Mechanisms That Help Organise Effective Synaptic Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$555,825.00
Summary
This study will test the idea that adhesion molecules alpha4- and beta2-laminin are needed for proper development and function of motor nerve - muscle connections. This study will provide insights into how such molecules control effective nerve-muscle communication, in both health and disease. We also believe that our results will provide the basic knowledge needed for identifying pharmacological targets that could improve such connections, and to promote reconnections between nerve and muscle.