Olfactory Ensheathing Cells: A Major Contributor To Axon Guidance?
Funder
National Health and Medical Research Council
Funding Amount
$575,749.00
Summary
The olfactory (smell) system is a unique part of the nervous system because nerve cells are generated throughout life. Understanding how the olfactory system grows and regenerates may lead to therapeutic approaches to repair other regions of the nervous system. This project will use high resolution digital time-lapse imaging of living nerve cells and the specialised cells called olfactory ensheathing cells to determine how the behaviour of these cells can be manipulated to improve regeneration.
One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movement ....One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movements. It is proposed that there are two parallel brain circuits involved in the analysis of motion, one tracking the movement of objects, and the other analysing a person s self-motion. Consider, for example, the task of a tennis player who has to return a serve. In order to achieve this, the brain must precisely integrate information about the ball s motion, as well as information about the player s speed and direction. This requires precise control of eye movements (to keep the eyes on the ball), as well as the ability to control the limb and trunk muscles. The aim of this study will be to map the anatomical framework underlying our ability to process all the relevant visual motion information, and to coordinate the appropriate motor responses. Such work is fundamental for understanding the functional organisation of the brain. It also has the potential to lay the groundwork for developments in areas of applied research, including medicine (e.g. the design of better rehabilitation strategies for people with brain damage), robotics- artificial intelligence (e.g. the improvement of artificial systems capable of vision), and the cognitive sciences (e.g. a better understanding of factors that limit human responses to visual stimuli).Read moreRead less
TRAFFICKING OF METABOLITES BETWEEN M LLER CELLS AND NEURONS IN DIABETIC RETINOPATHY.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and a ....Diabetes is the leading cause of blindness in the working population. In some diabetics, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an incease in growth factors from cells in the retina called Muller cells. Muller cells are vital for the normal function of the retina, and are known to be abnromal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in the early chnages seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better undetrstanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in diabetes will aid the development of more specific therapeutic agents in the future.Read moreRead less
Effects Of Saccadic Eye Movements On Perception And Visual Memory.
Funder
National Health and Medical Research Council
Funding Amount
$255,750.00
Summary
We all make rapid eye movements, called saccades, three times a second all our waking lives. They allow us to direct our gaze at what catches our attention, but they sweep images across our retinas and alter all the linkages between the eyes and the brain. The question at the heart of this project is how the visual system maintains perceptual stability given the disruption to the flow of visual input that saccades necessarily cause. It has to do more than suppress disturbing signals; it has to l ....We all make rapid eye movements, called saccades, three times a second all our waking lives. They allow us to direct our gaze at what catches our attention, but they sweep images across our retinas and alter all the linkages between the eyes and the brain. The question at the heart of this project is how the visual system maintains perceptual stability given the disruption to the flow of visual input that saccades necessarily cause. It has to do more than suppress disturbing signals; it has to link the present with the past. In recent years we and others have made substantial progress toward answering this question. In this project we plan a four-pronged attack that will take us further. We anticipate that our results will reveal how the visual system maintains and adjusts its representations of space and time, integrates signals from before and after saccades, and regulates the flow of information from memory to achieve a seamless melding of the present with the past. This project is not directed at any particular clinical problem, but disturbances of perception and memory are aspects of many clinical conditions. If we succeed in our aims what we discover will constitute a major scientific discovery which should find application to many conditions in which perception and memory are disturbed, from dyslexia to brain damage and even affective disorders such as schizophrenia and depression.Read moreRead less
Defining The Role Of EphA5 In Olfactory Axon Growth, Guidance And Fasciculation
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. In addition, we will also examine the behaviour of live cells as they are growing. In the past all attempts to understand how nerve cell connections are formed in the olfactory system have used dead tissue that has been permanently preserved. In this project we have the unique opportunity to visualise living nerve cells to enable us to determine how the cells react to the guidance signals. The advantage of this approach is that it allows us to identify important interactions as they occur, rather than attempting to decipher them after they have occurred. An analogy would be watching a football game live and observing how goals were scored and appreciating the performance of individual players versus trying to guess from the final score how the game was played and who the key performers were. The results of these experiments will provide important information on the regeneration of olfactory nerve cells, as well as on the initial growth and targeting of these nerve cells.Read moreRead less
Signalling Of Muscle Force By Golgi Tendon Organs During Exercise And Fatigue
Funder
National Health and Medical Research Council
Funding Amount
$181,320.00
Summary
It is a common experience for objects being carried to feel heavier and tasks needing muscular effort to become more difficult as one becomes tired and the muscles fatigue during exertion. The sensation of muscle force depends on two factors. One, a sense of the effort required to perform a task, is generated in the central nervous system and. The other, a sense of the force actually developed by the muscles, is generated in the muscles themselves by signals from sensory receptors called Golgi t ....It is a common experience for objects being carried to feel heavier and tasks needing muscular effort to become more difficult as one becomes tired and the muscles fatigue during exertion. The sensation of muscle force depends on two factors. One, a sense of the effort required to perform a task, is generated in the central nervous system and. The other, a sense of the force actually developed by the muscles, is generated in the muscles themselves by signals from sensory receptors called Golgi tendon organs. The sensation of muscle force and the heaviness of objects results from a combination of both senses, but the contribution of each is unknown. The aim of the project is to determine whether the disturbance of force sense in fatigued muscles results from changes in the way tendon organs signal the actual force developed by the muscles. This will be important for understanding how force sense is disturbed following exercise and in disease states, and for understanding the normal way muscle force is sensed in everyday situations. Disturbances of force sense after exercise will be documented in human subjects by asking them to generate what they perceive to be equal forces in both arms or legs, before and after one limb only is exercised. Errors in force estimation will show up as mismatches between the two limbs. The difficulty with human experiments is that the signals generated by tendon organs cannot be measured directly, but only inferred, perhaps wrongly. This difficulty will be overcome by measuring tendon organ activity directly in anaesthetised animals, where the muscles will be electrically stimulated to perform exercise similar to that in the human experiments. A change in tendon organ signalling will be taken to mean that similar changes in humans could be responsible for disturbances of force sense. In further experiments, the mechanism of the changes will be explored.Read moreRead less
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
Reflex Control Of Human Jaw Muscles By Periodontal Mechanoreceptors
Funder
National Health and Medical Research Council
Funding Amount
$405,173.00
Summary
An understanding of the functional connection between the jaw muscles and various receptor organs in and around the mouth is necessary to elucidate the process of chewing and its underlying rules. Unless the details of this functional connection in health and disease are thoroughly understood, the diagnosis and treatment of chewing related disorders will remain at the present state. For example: a We still do not know why chewing in edentulous subjects is less efficient and why the bite forces i ....An understanding of the functional connection between the jaw muscles and various receptor organs in and around the mouth is necessary to elucidate the process of chewing and its underlying rules. Unless the details of this functional connection in health and disease are thoroughly understood, the diagnosis and treatment of chewing related disorders will remain at the present state. For example: a We still do not know why chewing in edentulous subjects is less efficient and why the bite forces in these individuals immediately fall to about 20 % of the teethed value. Do jaw muscles in these subjects get weak because they get less support from the receptor organs around the teeth? a We still do not understand the cause-causes of the temporomandibular dysfunction (a painful disease involving jaw muscles) which forms 18.7 % of total dental patients consulted per week in South Australia. This South Australian study indicated that the current treatments (such as pain killers, night plates, massage) Ocures? only about the half of all patients. We cannot increase the success of the treatment if we do not fully understand the control mechanisms of chewing? It is expected that the results of this study will establish the functional connection between one of the most important receptor organs in the mouth (periodontal mechanoreceptors) to the jaw muscle motoneurons in subjects with healthy teeth and gums and will illustrate the importance of keeping the periodontium healthy for developing strong and smooth masticatory forces. This knowledge can also allow us to treat jaw related disorders by approaches that bring back normal operation of the system. For example, this knowledge may help us design active dentures that replace the missing support.Read moreRead less