Neural Plasticity Following Lesions Of The Central Nervous System In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$523,487.00
Summary
The brain and nervous system can adapt to injury and disease. The compensatory changes underlying this plasticity can ameliorate disability. This project will investigate the underlying mechanisms in patients with multiple sclerosis, by examining changes in the properties of nerve fibres in the peripheral nerve. The rationale for the project is that the properties of peripheral nerve fibres can reflect, at least in part, the properties of their cell bodies within the spinal cord.
Synaptic Integration And Plasticity In The Rat Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project i ....The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project is to begin by studying one of the simplest regions of the cerebral cortex, the olfactory (or piriform) cortex. The olfactory cortex is an evolutionarily ancient region of cortex, with a simpler architecture than other cortical regions. Its task is to process the sense of smell, a primitive sense that is more elaborated in lower animals than in humans. The broad goal of our research is to understand, by studying the olfactory cortex of rats, how olfactory processing occurs at the level of nerve cells (neurons). We will use a number of powerful techniques - including microelectrode recording and laser microscopy - to measure the electrical properties of individual neurons. We will also study the synaptic connections between neurons, and how these connections change following memory-inducing stimuli. It is hoped that this work will shed light on how the healthy cortex is able to process and store information, and how brain diseases cause these functions to deteriorate.Read moreRead less
I am a neuroscientist, who studies the neural mechanisms responsible for the control of human voluntary movements. My research is aimed at characterising the physiological mechanisms which are responsible for plasticity of the human motor cortical regions
Harnessing Human Motor Cortical Plasticity For Performance And Rehabilitation
Funder
National Health and Medical Research Council
Funding Amount
$341,304.00
Summary
Motor learning allows us to interact with our environment and loss of this ability is catastrophic. The reorganisational capacity of the brain can be used to enhance recovery from brain injury. However, our ability to do so is limited by lack of understanding of the underlying mechanisms. These studies will use novel approaches to investigate how the human brain reorganises during motor skill learning. The outcomes will be important for the development of novel therapeutic approaches.
Mechanisms Of Cortical Plasticity And Facilitation Of Functional Recovery Following Stroke
Funder
National Health and Medical Research Council
Funding Amount
$427,500.00
Summary
Specific regions of the human brain have been shown to reorganise following damage to the brain or peripheral nerves. This reorganisation is seen in both young and older subjects and is thought to be useful in helping to restore function. For example, following a stroke a patient may, initially, be unable to move one arm. However, in the following weeks and months some function may return. A number of mechanisms may be responsible for this improvement. However, it is likely that at least some of ....Specific regions of the human brain have been shown to reorganise following damage to the brain or peripheral nerves. This reorganisation is seen in both young and older subjects and is thought to be useful in helping to restore function. For example, following a stroke a patient may, initially, be unable to move one arm. However, in the following weeks and months some function may return. A number of mechanisms may be responsible for this improvement. However, it is likely that at least some of the improvement is due to reorganisation within the sensorimotor cortex. Following the stroke the control of the arm may be taken over by adjacent undamaged regions of the brain. This reorganisation allows impressive functional recoveries to occur. We have preliminary evidence to support the idea that patterns of activity generated in peripheral nerves (afferent input) following stroke may be crucial for the development of the organisational changes seen within the brain. We have shown that by applying specific patterns of sensory input we are able to produce organisational changes within the motor cortex of control subjects. Also, we have been able to induce similar changes in stroke patients. These changes have been accompanied by improvements in motor control. These novel and exciting findings support our hypothesis that by applying certain patterns of afferent input to patients following stroke we will be able to facilitate functional recovery by maximising reoganisation within the cortex. In the present project we will establish the organisation patterns in the brain of stroke patients and contrast the findings with control subjects. Secondly we will investigate the potential for facilitating recovery of stroke patients by the application of specific patterns of afferent input. These novel experiments may lead to important therapeutic developments that will benefit the large population of patients suffering strokes.Read moreRead less
The Contributions Of Different Sources Of Calcium To The Induction Of Long Term Potentiation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in ....When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in inducing increases in synaptic strength.Read moreRead less
Regulation Of Regeneration Of Dopaminergic Neurones In The Substantia Nigra
Funder
National Health and Medical Research Council
Funding Amount
$115,880.00
Summary
Parkinson's Disease (PD) results from the progressive loss of brain cells in the part of the brain called substantia nigra. These brain cells contain a chemical called Dopamine (DA). The symptoms of Parkinson's disease arise when about 80% these DA neurones are lost suggesting that some form of compensation must occur up to this point. In previous studies we have demonstrated that one mechanism for this compensation is through sprouting or branching of the remaining neurones. We have preliminary ....Parkinson's Disease (PD) results from the progressive loss of brain cells in the part of the brain called substantia nigra. These brain cells contain a chemical called Dopamine (DA). The symptoms of Parkinson's disease arise when about 80% these DA neurones are lost suggesting that some form of compensation must occur up to this point. In previous studies we have demonstrated that one mechanism for this compensation is through sprouting or branching of the remaining neurones. We have preliminary evidence about the way this is sprouting and regeneration is controlled. The aim of this grant is to explore in detail the mechanisms whereby sprouting is induced and regulated. The significance of this study is that it may provide insights into the way in which regulation of regeneration of the nervous system is controlled. It has specific applications to therapies for Parkinson's disease.Read moreRead less
Secretion Of Alpha-synuclein: A Diagnostic Marker For Parkinsons Disease And A Clue To Its (patho)physiology
Funder
National Health and Medical Research Council
Funding Amount
$634,051.00
Summary
We have found that a protein, alpha-synuclein is low in people with Parkinson's Disease. We wish to see if this can be used as a diagnostic test for the condition. Alpha-Synuclein is thought to be important in causing Parkinson's Disease. We suspect that by finding out why less of this protein enters the blood stream in Parkinson's Disease, we may discover clues as to how alpha-synuclein causes problems in this condition.
Neuropathways And Synaptic Adaptations Underlying Drug Addiction In Central Dopamine Systems
Funder
National Health and Medical Research Council
Funding Amount
$184,812.00
Summary
There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of ....There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of synaptic strength when excitatory inputs to DA cells are stimulated. These findings are important to drug addiction as amphetamine has been shown to block LTD and enhance LTP in brain slices of DA cells. Thus, changes in LTD and LTP by illicit drugs may underlie the conditions necessary for expression of drug-induced behavioural sensitisation, the best-accepted model of drug-craving in human addiction. To date, these studies have all been conducted in brain slices. Therefore, the functional importance of this synaptic plasticity in midbrain DA cells has yet to be shown in terms of changes in DA release in forebrain terminals in the living animal. For the first time we will address this issue by recording DA cell firing activity together with DA release using a newly developed technique that permits DA release to be monitored in the living brain in 'real-time' (100,000 samples-sec). This will allow us to identify the origin (cortical excitatory inputs) and receptor mechanisms that mediate LTP and LTD in DA cells and their effects on DA release. Recording DA cell activity with real-time measurement of DA release will promote a new cutting-edge technology to the Australian Neurosciences. These data will provide 'first of its kind' evidence of the functional anatomy and receptor mechanisms underlying synaptic plasticity in DA neurons associated with repeated drug use and ultimately enhance our basic understanding of the neural mechanisms of human drug addiction.Read moreRead less
Experience-dependent Maturation And Plasticity Of The Cerebral Cortex Mediating Schizophrenia-like Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$384,199.00
Summary
We will use genetic mouse models of schizophrenia to understand how specific abnormal behaviours are caused, focusing on cells and molecules within the brain. We will investigate how the gene mutations disrupts communication between, and production of, brain cells (neurons), and the role of mental and physical activity. The results of this project will not only have implications for understanding schizophrenia, but also for other brain disorders involving cognitive problems, such as dementia.