Targeting NPY Mechanisms In Rodent Models Of Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$437,637.00
Summary
This project will provide important information regarding the pharmacological mechanisms by which NPY acts to suppress seizures in animal models of epilepsy. It will provide strategies regarding potential new treatments of absence epilepsy.
We will use genetically engineered mice to study brain circuitry in an effort to understand the anatomical basis of Huntington's disease and a number of other more common degenerative brain diseases similar to Parkinson's disease. We will look at the brain in detail to decipher how the injured brain repais itself by making new connections and by producing new cells. We will also study supporting cells in the brain to determine if they play a beneficial role in this injury repair process.
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
Brain Adaptation Associated With Spontaneous And Training-induced Recovery Of Touch Sensation Post-stroke.
Funder
National Health and Medical Research Council
Funding Amount
$339,950.00
Summary
Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation ....Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation of the brain after stroke. Specifically we will: (i) locate areas of brain activity associated with natural and training-induced recovery of touch sensation following stroke and (ii) investigate the relationship between brain activation, sensory recovery and intervening experience. Site and extent of brain activation associated with recovery of touch sensation will be investigated over time using serial functional magnetic resonance imaging (fMRI), a controlled sensory task and clinical measures of recovery. Thirty stroke patients with impaired touch sensation of the upper limb will be studied at 2-6 weeks and 6 months post-stroke to investigate changes in brain activation associated with natural recovery (Study 1). Ten healthy controls will also be studied over 6 months. Those patients who still have sensory loss at 6 months will then receive specific sensory training or placebo intervention to study the effect of training-induced recovery on brain activity (Study 2). The whole brain will be studied and activation sites will be interpreted relative to individual and standard brain maps. We expect that the findings will advance our knowledge of the relationship between clinical recovery, training and neural plastic changes in the brain. This information will provide direction for the development of scientifically based treatments designed to maximise recovery and help identify patients who are likely to show natural recovery and-or benefit from training.Read moreRead less
Integrative Properites Of Intrinsic Sensory Neurons Of The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$211,681.00
Summary
For the neuronal control of the intestine to be appropriate to the constantly changing state of the organ, it is essential that there is feedback concerning, amongst other things, distension by its contents and its contractile state. These properties of the intestine are monitored by intrinsic sensory neurons, which are very special sensory cells, because they are embedded in the wall of the organ that they control. They have only very recently been identified, and thus surprisingly little is kn ....For the neuronal control of the intestine to be appropriate to the constantly changing state of the organ, it is essential that there is feedback concerning, amongst other things, distension by its contents and its contractile state. These properties of the intestine are monitored by intrinsic sensory neurons, which are very special sensory cells, because they are embedded in the wall of the organ that they control. They have only very recently been identified, and thus surprisingly little is known about how they perform their functions. It is clear, however, that they have special ways of integrating information about their environment, and the activities of other neurons, that are not shared by any other sensory neurons identified to the present time. Thus investigation of these neurons will provide information that is almost completely lacking about how the intestine performs its tasks. This information will be valuable in defining targets for development of therapeutic compounds and in analysing disorders of intestinal motility.Read moreRead less
Nanoparticle Based Neurotrophin Delivery To Promote Directed Neurite Growth And Auditory Nerve Rescue Following Deafness
Funder
National Health and Medical Research Council
Funding Amount
$506,724.00
Summary
The cochlear implant provides hearing information to the severe-profoundly deaf by electrically stimulating the auditory nerves of the inner ear. Deafness causes these auditory nerves to gradually degenerate leaving fewer nerves for the cochlear implant to stimulate. We propose to reverse this neural degeneration by delivering therapeutic drugs to the inner ear using tiny nanoparticles. This novel technology is expected to have application in other areas of neural degenerative disease.
Long Term Changes In Excitability Of Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$198,414.00
Summary
A large proportion of the community, about 20% at any one time, suffer from functional bowel disorders, the most common of which is the irritable bowel syndrome (IBS). The bowel in these patients appears normal; there are no overt changes in its appearance. However, the patients have discomfort, pain, abdominal bloating and altered bowel habits, which can include constipation and-or diarrhoea. There is general agreement that an alteration in the responsiveness of sensory neurons of the digestive ....A large proportion of the community, about 20% at any one time, suffer from functional bowel disorders, the most common of which is the irritable bowel syndrome (IBS). The bowel in these patients appears normal; there are no overt changes in its appearance. However, the patients have discomfort, pain, abdominal bloating and altered bowel habits, which can include constipation and-or diarrhoea. There is general agreement that an alteration in the responsiveness of sensory neurons of the digestive tract occurs in IBS. Until our recent discovery of long-term increases in excitability of intrinsic sensory neurons in the small intestine, no possible cellular basis for altered sensory neuron responsiveness that could underlie IBS had been found. We will investigate the mechanism of the long-term increase in excitability and will investigate drugs that are expected to modify its induction and-or maintenance. We expect that this work will aid in unravelling the genesis of IBS and will eventually lead to strategies to treat this common debilitating condition.Read moreRead less
Modulating Beta-amyloid Aggregation And Toxicity With Natural Metal-binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$399,243.00
Summary
Alzheimer's disease (AD) is a devastating disorder that afflicts millions of people worldwide. It is well established that the small peptide beta-amyloid, has a direct and important role in the development of AD. This project will investigate the ability of a small naturally occurring metal-binding protein to block the toxic actions of beta-amyloid.