A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Neural Mechanisms Underlying Human Grasp And Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$396,100.00
Summary
We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well ....We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well as in other neurological diseases such as neuropathies, nerve injuries, cerebral palsy and many others. The broad aim of this study is to investigate the poorly understood neural mechanisms that underlie sensorimotor control of hand function. We will target a specific aspect of manual dexterity that is crucial for the execution of common everyday tasks, like pouring liquid from a bottle, in which the digits are subjected to torsional loads. In order to maintain stable grasps, the motor control system must rapidly and automatically adjust the grip forces employed to meet the demands imposed by the changing torsion. This is only possible because of sensory feedback from the hand, a large component of which arises from the cutaneous mechanoreceptive afferent fibres. In the first two years we will use a combined approach of neural recording from peripheral nerves in anaesthetised monkeys and psychophysics experiments in normal humans to answer the general question: how does the population of cutaneous afferents provide precise feedback about torsion on the digits? In the third year we will perform key experiments in humans, using microneurography to record from their peripheral nerves. This will establish any differences between human and monkey mechanoreceptors.Read moreRead less
Modulating Retinal Glutamate Transport In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the m ....Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the mechanisms that regulate the concentration of glutamate in the retina. If these mechanisms could be made to work more efficiently, they may prevent the build-up of the glutamate and therefore prevent damage to the nerve cells. Understanding these mechanisms will aid in the development of an effective treatment to prevent blindness when there is a blockage of the blood supply to the retina.Read moreRead less
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less
Examining The Role Of ASIC Channels In Pain Through The Development Of Subtype-specific ASIC Channel Modulators.
Funder
National Health and Medical Research Council
Funding Amount
$617,256.00
Summary
Acid sensing ion channels (ASICs) sense changes in acidity in the body. They are found throughout the body and may underlie nerve damage in stroke and some types of pain. ASICs also have many as yet unknown functions. A lack of selective tools to study ASICs is a major barrier to a complete understanding of what they do. This proposal aims to modify three animal toxins which block these receptors to make useful tools to study their function, in particular their role in sensing pain.