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
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.
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
Amyloid Precursor Proteins Novel Role In Alzheimers Disease Through Regulating Neuronal Iron Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$949,667.00
Summary
Our group has discovered a novel role of amyloid precursor protein (APP) in cellular iron balance. The smallest form of APP, prevalently found in the brain, is able to convert a damaging iron variety (Fe2+) into the safer Fe3+. Alternative, larger, forms of APP are found to inhibit this effect. This project will establish how APP controls iron homeostasis within brain neuronal cells and how this activity is impaired in disease, thus development a mechanism for diagnostic tests and therapeutics.