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
The Functional Basis Of Direction Selectivity In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion ....Motion is an everday visual experience, and in this project we are attempting to explain how our brains are able to detect the direction in which an object is moving. Surprisingly this is first accomplished within the retina, the light-sensitive system of neurons at the back of the eye. Thus the eyes are able to tell the brain in which direction an object is moving. So the question becomes, how do the eyes do it? We know that there is a special class of neurons, the direction-selective ganglion cells, which are able to detect the direction of image motion. The activity of these cells is increased by excitatory connections and reduced by so-called inhibitory connections. This project aims to identify the neural origin of the inhibitory connections, and discover how the excitation and inhibition work together to compute the direction of motion.Read moreRead less
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
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
IDENTIFICATION AND FUNCTION OF RECEPTORS ON SYMPATHETIC TERMINAL SCHWANN CELLS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
The terminals of sympathetic nerves control many of the internal organs. Pharmacological intervention to promote or antagonize the effects of these terminals is very important in a number of different disease states of the autonomic nervous system. The present research proposal sets out to determine the way in which glial cells that partly envelop these terminals control their capacity to function.
Sulfonadyn-based Dynamin I-specific Inhibitors And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$835,291.00
Summary
Epilepsy affects 1% of people, yet 30% do not respond to anti-epileptic drugs (AEDs). Traditional drug discovery fails to improve this situation. Our team discovered dynamin as a new target for better AED design and our lead sulphonadyns reduces seizures in animals. We will design better sulfonadyns that can ultimately be used for clinical trials by designing the drugs away from its actions outside of neurons. If successful, this will accelerate new AED development with less side-effects.
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
Modulation And Trafficking Of SK Channels In The Lateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$260,980.00
Summary
The amygdala is a brain structure that underlies emotional processing. Malfunctions in emotional processing are thought to be the cause of anxiety disorders. Understanding amygdala physiology is thus vital for developing therapies to treat these disorders. We have recently found a novel role for an ion channel in controlling amygdala excitability. In this grant we will investigate how this ion channel is modulated, which will elucidate a novel way in which activity in the amygdala is regulated.