How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Imaging Atlases Of The Brain Of Humans And Experimental Animals
Funder
National Health and Medical Research Council
Funding Amount
$808,375.00
Summary
This project uses imaging techniques and molecular genetics to produce the next generation of brain maps. It will advance our understanding of the organisation and structure of the brain and spinal cord of humans and experimental animals – paving the way for the development of psychotherapeutic drugs and more accurate interventions on the human brain. The new maps will help those who study the brain of patients with diseases such as Alzheimer’s or Parkinson’s or animal models of these diseases.
Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, litt ....Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, little is known of the response properties, structure and organization of receptors and neurones responding to, and relaying information about painful stimuli, from bone to the brain. The objectives of this project are to reveal the fundamental neural mechanisms that account for the perception of bone pain. The project will test a series of specific hypotheses in order to explain why bone pain is often poorly controlled by standard pharmacological or surgical approaches. It is expected that this study will reveal the neural mechanisms responsible for relaying sensory information, in particular, that regarding painful stimuli, from bone to the brain. It will lead to a better understanding of the mechanisms of bone pain and form the template for future studies of its treatment.Read moreRead less
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain devel ....Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate the way in which the multiple visual areas of the brain develop and become 'wired' together in the period following birth. We will also determine if there are mechanisms which allow alternate routes to be found for processing visual information while the brain is still establishing connections between its multiple areas. This will allow us to understand the anatomical and physiological bases of the deficits caused by early damage to the visual areas of the brain, and perhaps point to strategies that will lead to improved recovery of visual function.Read moreRead less
Neurogenic Hypertension In The Spontaneously Hypertensive Mouse : Role Of The Hypothalamic-brainstem Sympathetic Axis
Funder
National Health and Medical Research Council
Funding Amount
$475,917.00
Summary
In human high blood pressure, particularly in the young, an overactive nervous system is thought to be a major underlying cause. Using a unique mouse model of high blood pressure which closely resembles this aspect of the human disease, we will examine which brain cells and neuro- chemicals are involved, particularly in a small area that is involved in regulating the hormonal and nervous system response to stress. From this we hope to be able to target these chemicals with specific therapy.
G-alpha Proteins And Their Effectors (AC, PLC, Rho And ERK) In Central Cardiovascular Regulation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,716.00
Summary
High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific protei ....High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific proteins within cells, which are important in cell to cell communication in the brain, have in the control of blood pressure. Cells in the brain communicate using chemical messengers that act at receptors on the cells surface. Three forms of these receptors exist. We are interested in the most abundant form of receptor that has about 860 members. When activated these receptors use a complex cascade of proteins within the cell to dictate that cell's response. We know that some of these receptors in the brain are involved in the regulation of blood pressure and that some of them are altered in conditions such as hypertension. We could target each of the receptors but for many of them we do not know the chemical than activates them. Fortunately each of 860 receptors act primarily via just a few specialised proteins. Initially we will target these proteins to determine the impact these receptors have in altering the resting levels of blood pressure, their role in response to stimuli that affect blood pressure and the role they play in hypertension. Three approaches will be used: altering function of the proteins, identifying the types of proteins present and identifying the cells involved, in brains sites important in regulation of the heart and blood vessels. This novel approach to understanding how the brain controls blood pressure will undoubtedly identify targets for novel blood pressure lowering therapies and targets for genetically determined causes of hypertension.Read moreRead less
I am a neuropharmacologist and a neuroanatomist who is involved in utilising a multidisciplinary approach to investigate the functional role of metalloproteinases in the brain.
Forebrain Neuroadaptations To Chronic Morphine Treatment
Funder
National Health and Medical Research Council
Funding Amount
$435,956.00
Summary
Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerv ....Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerve cells in the brain. The affected nerve cells are responsible for causing new behaviours that appear once addiction is established. Addiction is not exclusive to humans. Animals will self-inject the same addictive drugs that humans use, and show many other kinds of addictive behaviours that parallel aspects of human addiction. Studying the effects of addictive drugs on rats and other animals has been very important in working out where and how drugs work. We now have a very good idea of which parts of the brain are affected by drugs, and it turns out that most addictive drugs act in the same places. We also now know for all of the major drugs, exactly which parts of nerve cells they affect. However, this turns out to be only the first step as the nerve cells that directly respond to drugs can affect other whole networks of nerve cells. This study is going to look at how morphine, a drug that is related to heroin, affects nerve cells in a part of the brain that helps cause addiction. It is going to work out which of the many pathways in this brain region are affected by morphine treatments that cause addiction in rats. It will then see what is happening to single nerve cells in the affected pathways. If we can understand more about these processes it may become possible to come up with new ways to treat addiction. We will also understand much more about the production of powerful emotional and behavioural drives so many of us find hard to control.Read moreRead less