Cellular Mechanisms Underlying The Sense Of Balance
Funder
National Health and Medical Research Council
Funding Amount
$192,960.00
Summary
Dizziness, vertigo, and imbalance are major reasons for visits to the doctor, particularly by the elderly. For example, balance related falls account for an astonishing 50% of accidental deaths in people over 65. Inner ear disturbances account for 85% of these cases. Illness, infections, disease, head trauma or simply the natural aging process cause these disturbances and it is thought that they result in abnormal signals being sent from the inner ear to the brain. In spite of the health costs a ....Dizziness, vertigo, and imbalance are major reasons for visits to the doctor, particularly by the elderly. For example, balance related falls account for an astonishing 50% of accidental deaths in people over 65. Inner ear disturbances account for 85% of these cases. Illness, infections, disease, head trauma or simply the natural aging process cause these disturbances and it is thought that they result in abnormal signals being sent from the inner ear to the brain. In spite of the health costs associated with disorders of balance, very little is known about how signals are generated in our vestibular organs, let alone what abnormal changes may occur. Our attempts to understand balance in humans have been hampered by the lack of suitable experimental models. This proposal takes advantage of a newly developed mouse preparation to study key problems that could not be realistically addressed in whole animal or dissociated cells. We will investigate three critical components of balance organs. These components are: 1) hair cells that detect motion; 2) nerve endings that send information from hair cells to the brain; and 3) nerve endings that bring information from the brain. The aim of this proposal is to understand how these components interact with each other to provide us with a sense of balance. This knowledge will be the first of its kind and contribute significantly to our understanding of human vestibular function and pathology.Read moreRead less
Gastrointestinal Sensory Function In Normal And Diseased States
Funder
National Health and Medical Research Council
Funding Amount
$691,026.00
Summary
Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that ....Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that reduce specific types of sensory signals from the gut. We shall investigate sensory mechanisms in the upper and lower regions of the gut, where symptoms are most prevalent in diseases such as non-cardiac chest pain, functional dyspepsia and irritable bowel syndrome. Six aspects of sensory nerve endings in the gut are to be investigated: 1. The grouping of endings into functional classes (similar to touch or pressure receptors in skin) 2. How endings respond to chemicals and hormones found in the gut 3. How currently available drugs may be useful in reducing sensitivity 4. The mechanisms by which inflammation affects sensitivity 5. How nerve growth factors may trigger changes in sensitivity 6. How pores or channels in nerve endings determine their functionRead moreRead less
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
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less
The Role Of Afferent Input In The Development Of Focal Task Specific Dystonia
Funder
National Health and Medical Research Council
Funding Amount
$213,000.00
Summary
The term dystonia is used to describe a condition that is characterised by abnormal muscle activation patterns. This leads to impaired control of voluntary movements. Depending upon which part of the body is affected, dystonia may be classified as generalised (affecting two or more body segments), hemi (involving one side), segmental (involving adjacent body parts or a segment), or focal (affecting one part of the body). Many of the focal dystonias are also task specific and the aim of this prop ....The term dystonia is used to describe a condition that is characterised by abnormal muscle activation patterns. This leads to impaired control of voluntary movements. Depending upon which part of the body is affected, dystonia may be classified as generalised (affecting two or more body segments), hemi (involving one side), segmental (involving adjacent body parts or a segment), or focal (affecting one part of the body). Many of the focal dystonias are also task specific and the aim of this proposal is to investigate these task-specific focal dystonias. Task-specific focal dystonia is common in the community and causes considerable suffering and loss of productivity. For example, writer's cramp (a common form of task specific focal dystonia) is probably the commonest cause of writing difficulty in patients in whom this is the sole complaint. No treatment regimen has been shown to be effective in alleviating it's often debilitating symptoms. The aim of these studies is to further define the pathophysiological changes seen in task-specific dystonia and investigate the mechanisms responsible for their generation. Using the techniques of transcranial magnetic stimulation and peripheral nerve stimulation we will investigate the organisation of the motor cortex in this condition and examine the influence of afferent input on intrinsic cortical circuitry. We hypothesise that the motor regions of the brain are more sensitive to the particular repeated patterns of sensory information reaching the brain during repetitive movement and this results in abnormal alterations in organisation that may be responsible for the symptoms of dystonia. Additionally, we predict that it may be possible to reverse these organisational changes by applying novel patterns of nerve stimulationRead moreRead less
Mechanosensitive Afferent Nerves And Gastrointestinal Motility
Funder
National Health and Medical Research Council
Funding Amount
$384,693.00
Summary
This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory ne ....This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory nerves there are and whether they all respond to stretch in the same way. We cannot identify their specialised endings in the wall of the gut. While these sensory nerves definitely respond to stretch, they are also known to respond to contractions of the gut wall. Despite this, we do not understand how the normal movements of the gut wall activate them, nor why some movements can lead to pain. Most of the experiments will be carried out on small pieces of tissue taken from humanely killed guinea pigs and studied, under highly controlled conditions, in organ baths. The remainder of the study will be on specimens of human gut tissue obtained at surgery. This project will use new techniques to record sensory nerves during both stretch and contraction of the gut wall to understand what activates them. In addition, their endings will be labelled with dye to reveal their different shapes. Using computerised imaging techniques we will identify whether they respond to particular patterns of movement in the gut wall. Lastly we will record from these sensory neurones in live specimens of human colon to see whether the same types of sensory nerves are present in humans as in the small animals. This study will provide the first comprehensive account of sensory nerves to the gut wall that respond to distension, including those that activate pain pathways. This is a pre-requisite for designing new drugs that will target these nerve cells with minimal side effects.Read moreRead less