Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
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
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related ....Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related disease such as heart attack and stroke. Thus this research proposal is of special relevance to National Research Priority 2: Promoting and Maintaining Good Health. Obesity and obesity-related medical conditions particularly affect older people, so that our research is also highly relevant to National Research Priority 2 sub-areas: Ageing well, Ageing productively.Read moreRead less
Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundament ....Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundamental insights and conceptual advances into how autonomic function is controlled by the brain will provide a better understanding of these fundamental processes and will contribute to Australia’s priority research areas to improve health and advance product development.Read moreRead less
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.
Exploring the brain mechanisms underlying hyperactivity in Attention-Deficit/Hyperactivity Disorder. Attention-deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder affecting children, resulting in substantial costs (both human and financial) to the child, their family and Australian society. The outcomes of this project will provide a better foundation for understanding dysfunctional brain mechanisms in AD/HD, which is expected to lead to better diagnosis, treatment, an ....Exploring the brain mechanisms underlying hyperactivity in Attention-Deficit/Hyperactivity Disorder. Attention-deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder affecting children, resulting in substantial costs (both human and financial) to the child, their family and Australian society. The outcomes of this project will provide a better foundation for understanding dysfunctional brain mechanisms in AD/HD, which is expected to lead to better diagnosis, treatment, and community support. Ultimately this will contribute to a healthy start to life for these children. This project will also demonstrate how an integrated Australian approach can lead the research agenda in both basic neuroscience, at the interface of psychology and physiology, and its applications in health.Read moreRead less
Towards a continuum model of orienting and defensive responses. Orienting (OR) and Defensive Responses (DR) underlie important survival functions of attending to unexpected stimuli and avoiding harm.We will establish the first integrative profile of human OR/DR function, using simultaneous recording of brain activity and 'body' responsivity. Given sex and age variation in OR/DRs, both males and females spanning six decades will be studied. OR/DR abnormalities are associated with major disorders ....Towards a continuum model of orienting and defensive responses. Orienting (OR) and Defensive Responses (DR) underlie important survival functions of attending to unexpected stimuli and avoiding harm.We will establish the first integrative profile of human OR/DR function, using simultaneous recording of brain activity and 'body' responsivity. Given sex and age variation in OR/DRs, both males and females spanning six decades will be studied. OR/DR abnormalities are associated with major disorders of attention and stress, which also vary with sex and age. We will examine relationships between OR/DR function and proneness to these disorders in healthy individuals. The results will provide a framework for developing prevention and intervention strategies.Read moreRead less
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.
Functional tracing of brain circuitry by a novel approach. A genetically modified virus is taken up by axon terminals (the 'output' part of a nerve cell) and transported by the cell back to the cell body (its 'input' part). Once there, it makes a protein that makes the cell sensitive to blue light. This new tool may be instrumental in answering questions about nerve connections that cannot be answered in other ways.