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.
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.
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
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.
Optimising And Applying Ocular Vestibulat Evoked Myogenic Potentials (oVEMPs)
Funder
National Health and Medical Research Council
Funding Amount
$228,931.00
Summary
This project seeks to optimise techniques for a new method of assessing the balance organs (vestibular organs) and then apply these techniques. Three conditions will be studied: vestibular neuritis - a condition causing acute and severe dizziness; Parkinson's disease, in which disorders of balance are common and superior canal dehiscence (SCD) in which there is a hole in the bone overlying one of the semicircular canals, leading to sensitivity to sound.
The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated ....The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated appreciably in the past. We believe that these sensory neural circuits will reveal important new insights into how internal organs perform their diverse and essential functions to sustain life.Read moreRead less
Hypothalamic Oxexin-synthesizing Neurons Regulate The Ultradian Basic Rest-Activity Cycle (BRAC); Studies In Transgenic Rats And Mice
Funder
National Health and Medical Research Council
Funding Amount
$588,418.00
Summary
In the hypothalamus region of the brain there is a group of neurons that synthesize a neuropeptide messenger called orexin. In humans, malfunction of orexin neurons results in narcolepsy (abnormal sleepiness) and in disordered metabolism resulting in obesity. Our experiments, conducted in genetically-modified rats and mice, will elucidate the manner in which the orexin neurons integrate our behaviour (eg eating) with our physiological state (eg body and brain temperature, arterial blood pressure ....In the hypothalamus region of the brain there is a group of neurons that synthesize a neuropeptide messenger called orexin. In humans, malfunction of orexin neurons results in narcolepsy (abnormal sleepiness) and in disordered metabolism resulting in obesity. Our experiments, conducted in genetically-modified rats and mice, will elucidate the manner in which the orexin neurons integrate our behaviour (eg eating) with our physiological state (eg body and brain temperature, arterial blood pressure).Read moreRead less