Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
How Does Chronic Epilepsy Result In Cardiac Electrophysiological Dysfunction?
Funder
National Health and Medical Research Council
Funding Amount
$737,112.00
Summary
Cardiac dysfunction is common in epilepsy, and could be an important contributor to the increased risk of sudden death in people with epilepsy (SUDEP). In this grant we will investigate: when changes in the cardiac function develop in relation to the epilepsy; if people with chronic epilepsy have similar changes; and what effect seizures and epilepsy has on the nerves innervating the heart. The outcomes have the potential to motivate new treatments and prevention for this important problem.
A Brain-based Model Of Anxiety Sensitivity In Panic Disorder
Funder
National Health and Medical Research Council
Funding Amount
$402,214.00
Summary
This project will combine advanced brain imaging and brain network modelling to better understand the neurobiology of panic disorder with relevance to its treatment.
Probing Neural Circuits Of Emotion With Ultrafast FMRI And Dynamic Natural Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$306,012.00
Summary
Emotion is central to our everyday experience and forms the backbone of our social relationships. Our understanding on emotion, however, mostly relies on strictly controlled task designs, using highly simplified and/or artificial stimuli. In this project, we propose a new platform to study brain activity underlying natural emotional experience. The design and methodology developed in this proposal will provide fundamental outcomes for understanding emotion disturbances in mental disorders.
Brain Pathways For Neurally-mediated Fever: From Vagal Afferent To Sympathetic Output To Brown Adipose Tissue Via Brain
Funder
National Health and Medical Research Council
Funding Amount
$405,223.00
Summary
Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins ....Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.Read moreRead less
Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (de ....Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (defecation/urination) functions are coordinated. The expected outcomes are predicted to aid future discovery of mechanisms of cross-organ sensitisation and are anticipated to provide significant benefit to therapy development for chronic visceral pain syndromes associated with bowel and bladder dysfunction.Read moreRead less
Differential Regulation Of Human Tyrosine Hydroxylase Isoforms And The Development Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$325,591.00
Summary
Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than othe ....Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than other dopaminergic cells in the brain. Tyrosine hydroxylase controls the rate of dopamine synthesis. Humans are unique in that they contain four isoforms of tyrosine hydroxylase and therefore they have the potential to alter the regulation of dopamine synthesis in ways that other species do not. Recent developments in our laboratories have suggested that particular isoforms of tyrosine hydroxylase may have either a role in the susceptibility of dopaminergic neurons to degeneration in Parkinson's disease or a role in the timing of the symptoms of the disease. We have demonstrated differences in the distribution of the human TH isoforms within the substantia nigra, with certain isoforms being more prevalent in the susceptible ventral cells. We have also shown that there are major differences in the regulation of the four human tyrosine hydroxylase isoforms. Some isoforms will be more sensitive to conditions that occur with high frequency stimulation of neurons and some to low frequency sustained stimulation. This would provide a mechanism by which differential distribution of the human TH isoforms would result in altered dopamine synthesis in different parts of the human brain and this may in turn lead to either increased susceptibility to, or earlier appearance of symptoms of, Parkinson's disease.Read moreRead less
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.
Effectiveness Of Ghrelin Receptor Agonists To Limit The Extent Of Tissue Damage Caused By Traumatic Injury To The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$592,002.00
Summary
Ghrelin is a naturally occurring compound that under adverse conditions can activate specific receptors on cells around the body to enhance their survival. These receptors are also present in the spinal cord, but ghrelin doesn't enter the spinal cord. We will investigate a new group of compounds that can enter the spinal cord and activate these receptors to see if this can reduce the amount of damage that occurs after a spinal cord injury. Less tissue damage would mean less permanent disability.