I am a neurophysiologist interested in brain regulation of homeostatic and autonomic functions in health and disease. I am endeavouring to discover the brain pathways for these vital functions, and to translate my findings from animal research to humans.
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
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.
The Amygdala And Emotionally-mediated Sudden Cutaneous Vasoconstriction In Rats
Funder
National Health and Medical Research Council
Funding Amount
$461,788.00
Summary
Discovering how the brain organizes our emotional life is important for understanding mental illness. In rats, blood flow to the skin falls when the animal detects a possibly dangerous event. Rats go pale with fright , just as humans do. The falls in blood flow are inhibited by drugs used to treat people with schizophrenia. The grant investigates whether the amygdala is an important brain centre controlling the skin blood vessels, and whether anti-schizophrenia drugs act in the amygdala.
Human Hypothalamic Homologues To Autonomic Control Centres Identified In Rat And Monkey
Funder
National Health and Medical Research Council
Funding Amount
$358,770.00
Summary
The hypothalamus is a brain structure common to all mammals. Experiments on the rat have shown the hypothalamus to be fundamentally involved in cardiovascular control, fluid and electrolyte balance, food ingestion and energy metabolism, thermoregulatory and immune responses, and defensive-aggressive responses and reproduction. It is virtually impossible to perform functional studies in the human and, therefore, the human hypothalamic regions involved in these functions will be inferred from thei ....The hypothalamus is a brain structure common to all mammals. Experiments on the rat have shown the hypothalamus to be fundamentally involved in cardiovascular control, fluid and electrolyte balance, food ingestion and energy metabolism, thermoregulatory and immune responses, and defensive-aggressive responses and reproduction. It is virtually impossible to perform functional studies in the human and, therefore, the human hypothalamic regions involved in these functions will be inferred from their structural similarity to the centres identified in the rat. The present project will obtain structural-chemical data on the rat and monkey for the sole purpose of comparing these data with similar data on the human. The parts of the hypothalamus that deal with cardiovascular and other autonomic functions are expected to be similar in the rat and human and the present study will identify in the human all major regions that have been identified in the rat. The correspondence between an area in the rat brain and one in the human brain will be established primarily on the basis of chemical similarity. Corresponding areas tend to feature similar neurotransmitters, enzymes and other neuroactive substances. Some of the chemicals to be investigated are known to have a role in autonomic control. The chemical mapping study then serves two roles: (a) It permits the identification of the chemical profile (signature) of an area and consequently enables its identification in the human, and (b) it reveals the chemicals the area utilizes for possible theoretical and practical considerations. The present study will allow hypotheses derived from experimental work on the rat to be more meaningfully tested on humans. It will assist pathological and imaging investigations of the human brain.Read moreRead less