Forebrain Control Of Cardiovascular Function: Integrative And Cellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$834,233.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what causes this increased sympathetic activity, but one possibility is that it is due to the action of a circulating hormone called angiotensin, which acts on the brain, activating central nerve pathways which ultimately increase sympathetic activity. In this project we aim to test this hypothesis and thus help to unravel the mechanisms involved in the long term control of sympathetic activity and blood pressure.Read moreRead less
PURINERGIC TRANSMISSION AND CENTRAL AUTONOMIC REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$157,848.00
Summary
The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to mo ....The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to modulate blood pressure and heart rate. This project is designed to characterise the mechanism by which purines act within specific brain nuclei to regulate the cardiovascular system. Considering the large economic burden on the healthcare system caused by cardiovascular disease, this research is vital to increase our understanding of how diseases such as hypertension may be caused, and therefore provide improved therapeutic strategies.Read moreRead less
Neuroendocrine Responses To Psychological Stress: Unmasking The Protective Role Of The Prefrontal Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$346,153.00
Summary
This project seeks to build up a picture of one of the mechanisms that the brain uses to protect our bodies from the potentially harmful effects of psychological stress. When we are subjected to psychological stress one of the consequences is the release of a hormone, corticosterone, into the blood-stream. This can be beneficial in the short-term as it helps our body redistribute its pattern of energy utilization in a way that helps in coping with an unexpected challenge. However, excessive secr ....This project seeks to build up a picture of one of the mechanisms that the brain uses to protect our bodies from the potentially harmful effects of psychological stress. When we are subjected to psychological stress one of the consequences is the release of a hormone, corticosterone, into the blood-stream. This can be beneficial in the short-term as it helps our body redistribute its pattern of energy utilization in a way that helps in coping with an unexpected challenge. However, excessive secretion of corticosterone due to excessive exposure to psychological stress can damage your health. For example, it can make you more susceptible to infection and also accelerate the rate at which your brain ages. The brain possesses certain mechanisms which try to limit the release of corticosterone when you are subjected to psychological stress. Unfortunately these mechanisms are not quite up to doing the necessary job under the conditions in which we live today, i.e. a very high level of psychological stress is a common feature of modern life. Nevertheless we believe that if we can properly understand these protective mechanisms in the brain, it may be possible to develop drugs which can boost their efficiency. In the long term this could greatly reduce ill-health in our society.Read moreRead less
IDENTIFICATION OF BRAIN NEURONS INVOLVED IN THE CARDIOVASCULAR RESPONSE TO FEAR AND FLIGHT
Funder
National Health and Medical Research Council
Funding Amount
$400,247.00
Summary
The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vess ....The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vessels which restrict the flow of blood to the tissues. These nerves, in turn, are under the control of brain cells or neurons which are located in the brainstem. Blood pressure-controlling neurons, acting upon information they receive from pressure sensors in the major blood vessels in the chest cavity, can alter their activity so that blood pressure is maintained within normal limits. Our laboratory has been examining the properties of these blood pressure-controlling neurons by recording their minute electrical discharges and by studying other brain regions which are able to influence them. In this study, we will use newly-developed procedures which will allow us to identify the precise locations of these neurons in the brain, to study which neurotransmitters (chemicals released by neurons which are used to communicate with other neurons) they use, as well as to identify other regions of the brain they connect with and influence. The major significance of this work will be that new brain circuits which transmit information about the status of the cardiovascular system to other areas of the brain will be identified. Our understanding of, and the development of new treatments for, cardiovascular diseases such as high blood pressure and heart failure are critically dependent on advancing our understanding of the nervous system.Read moreRead less
Roles Of Brain-derived Neurotrophic Factor In The Regulation Of Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to ....Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to analyse physiological roles of BDNF in the brains stem and spinal cord in the regulation of nerve activity and blood pressure. The successful execution of the project will significantly enhance our understanding of how blood pressure is controlled by BDNF and nerve activity. The knowledge from this study will form basis for designing new drugs to control high blood pressure.Read moreRead less
Functional Mapping Of Autonomic Control Circuits In The Human Brain
Funder
National Health and Medical Research Council
Funding Amount
$291,451.00
Summary
Nerves called sympathetic nerves stimulate the heart and raise blood pressure. The brain drives them when we are excited or frightened. It also over-drives them in cardiovascular diseases, and this makes matters worse. This project will use MRI brain scanning to investigate, for the first time, how the cerebral cortex and brain stem act together to control sympathetic nerves. Understanding how this system works normally will help tell us how it may malfunction, and what we can do to correct it.
PREMOTOR SYMPATHETIC CONTROL OF BLOOD PRESSURE DURING PSYCHOLOGICAL STRESS: HYPOTHALAMUS VERSUS MEDULLA.
Funder
National Health and Medical Research Council
Funding Amount
$153,616.00
Summary
Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known ....Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known as psychological stress and it is usually associated with anxiety. Unfortunately, it is also the most common form of stress in modern urban life. There are clear indications that when these autonomic changes become chronic they can lead to hypertension, weak immune responses and gastric ulcers. In people already suffering from cardiovascular diseases they can also precipitate cardiac and cerebrovascular accidents. Clearly, the link between psychological stress and the autonomic nervous system needs to be explored in more detail. This project looks at the organization of the neural network in the brain and spinal cord that controls these responses. It uses a simple model of psychological stress in the conscious rat and recent non invasive techniques to record blood pressure and look at neuronal activity. We think that we have identified a group of neurons that may be controlling very specifically this response. It is located in the hypothalamus. The aim of this project is to further test the role of these neurons and find out what is controlling them. They will also be compared to another group of neurons that also controls blood pressure but apparently not in relation to psychological stress. The possibility that the cardiovascular response to psychological stress might be mediated by a specific group of neurons in the brain is a very exciting finding. It could lead to new therapeutic applications for acting against the short and long term effects of stress.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less