Neural Circuits For Odour-processing In The Rodent Piriform Cortex 'in Vivo'
Funder
National Health and Medical Research Council
Funding Amount
$488,817.00
Summary
We are studying the brain circuits that enable mammals to recognise odours. We will apply puffs of odorants to the nose of an anaesthetised mouse while measuring electrical signals in the odour-processing region of its cerebral cortex. Our work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the world. This is basic research that will, in the longer term, shed light on the disturbances that occur during mental illness.
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.
Persistent Firing In Cortical Interneurons: Mechanisms And Potential Anticonvulsant Role
Funder
National Health and Medical Research Council
Funding Amount
$520,552.00
Summary
The normal brain treads a fine line between too much electrical activity (epilepsy) and too little (sedation). We have discovered a class of brain cell that seems to behave like a sentinel, monitoring brain activity for signs of epilepsy. If a seizure occurs, this cell switches on an electrical brake that dampens excess activity. In this project we will study how this brake works and whether it really can inhibit seizures. Our research may lead to better treatments for epilepsy.
Astroglial Remodelling Of The Interhemispheric Midline Is Regulated By Deleted In Colorectal Cancer (DCC) Signalling And Is Required For Corpus Callosum Formation
Funder
National Health and Medical Research Council
Funding Amount
$669,400.00
Summary
The integration of information between the brain hemispheres occurs via a large bundle of connecting nerve fibres called the corpus callosum. People with a genetic mutation in DCC display mirror movement disorder and some have a severe brain defect where the corpus callosum fails to form, but at present we don’t understand the function of this gene. In this study we will investigate how DCC functions in early brain development to regulate corpus callosum formation and mirror movement disorder.
Properties Of Dendritic Spines And Their Role In Synaptic Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Connections between nerve cells in the brain often occur onto enlarged protrusions called dendritic spines. This proposal will investigate the properties of dendritic spines, and relate differences in spine properties to synaptic plasticity. This information can be used to better understand and treat neurological disorders associated with spine malfunction, as occur in some forms of mental retardation, and may help with understanding the memory loss that occurs during ageing and dementia.
Excitability And Hyperexcitability Of Neural Circuits In The Rodent Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$371,807.00
Summary
We are studying the properties of neurons (nerve cells) and brain circuits that enable mammals to recognise and remember odours. Our experiments will focus on neurons in the odour-processing region of the cerebral cortex of mice. This work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the external world. Our findings will also provide a deeper understanding of the causes of epilepsy, leading to improved treatments.
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
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
Metabolism And Neurotoxicity Of Hemin And Hemin-derived Iron
Funder
National Health and Medical Research Council
Funding Amount
$346,400.00
Summary
Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metaboli ....Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metabolism of hemin by the different types of brain cells. The present project investigates the metabolism and neurotoxicity of hemin in brain cells and will examine the capacity of potential therapeutic agents to protect brain cells from hemin toxicity. The data obtained from this project will advance our understanding of the uptake and metabolism of hemin by the four main types of brain cell, and the factors that are likely to be involved in the neurotoxicity of hemin-derived iron following hemorrhagic stroke. The study will also provide data concerning the relative effectiveness of potential therapeutic agents, and information concerning the cell types, time points and aspects of hemin metabolism that are most effectively targeted by these agents. Such advances will guide the development of therapeutic approaches that are directed at minimising the brain damage which results from hemin-derived iron in humans.Read moreRead less
Disorder in the circuits that process emotional stimuli are central in the pathogenesis of anxiety disorders. In this grant we will study the circuits that are inolved in fear learnng. Our results will provide the background to developing more effective therapies for a range of anxiety related disorders such as generalised anxiety and post traumatic stress disorder.