Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
Mechanisms Controlling Sympathetic Nerve Activity To The Heart
Funder
National Health and Medical Research Council
Funding Amount
$101,220.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart and the kidney that has detrimental effects which is related to mortality in patients. The areas in the brain causing the increased nerve activity to the heart are unknown. We will investigate the role of two key brain areas in mediating this increase. In addition we will also focus on local mechanisms that are responsible for the increase in noradrenaline spillover.
Investigations Of Neural Pathways For Heat Loss And Heat Gain In Thermoregulation And Fever
Funder
National Health and Medical Research Council
Funding Amount
$349,486.00
Summary
This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the gener ....This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the generation of heat from fat tissue in response to cold or fever with those controlling blood flow to the skin. These nervous pathways may be critical for maintaining correct body temperature during general anaesthesia, infections or in the aged subjected to temperature extremes. Thus, they are of importance in the health and well-being of much of the population.Read moreRead less
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
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
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
Discovery Early Career Researcher Award - Grant ID: DE230101079
Funder
Australian Research Council
Funding Amount
$453,528.00
Summary
New insights into how the brain interprets visceral and somatic sensations. Sensory nerve fibres monitor normal and abnormal stimuli in our body tissues, sending this information to the brain. I study the sensory pathways of the respiratory system which protect the lungs from harmful stimuli, such as inhaled pollutants or smoke. I discovered that respiratory sensory pathways interact with sensory circuits in the brain arising from other body tissues. The goal of this project is to investigate on ....New insights into how the brain interprets visceral and somatic sensations. Sensory nerve fibres monitor normal and abnormal stimuli in our body tissues, sending this information to the brain. I study the sensory pathways of the respiratory system which protect the lungs from harmful stimuli, such as inhaled pollutants or smoke. I discovered that respiratory sensory pathways interact with sensory circuits in the brain arising from other body tissues. The goal of this project is to investigate one example of this interaction; the convergence of visceral and somatic sensory pathways onto a brain circuit that regulates the intensity of the sensations that are experienced. This project addresses the fundamental question of how the brain processes two competing noxious sensations.Read moreRead less
Imaging The Activation Of Sensory Nerve Endings That Detect Pain In The Colorectum
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Within the gastrointestinal tract are sensory nerve endings that detect painful stimuli. In this project a new technique has been developed that allows us to monitor and record the activation of the particular sensory nerve endings that detect painful stimuli. This project will determine how these sensory nerve endings detect pain and how drugs might be used to relieve these unpleasant sensations arising from the gut wall.
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