The Role Of The Orbitofrontal Cortex In Disorders Of Response Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$515,488.00
Summary
We will investigate the role of the orbitofrontal cortex (OFC) in decision-making, particularly the effect of hyperactivity in the medial vs. ventrolateral orbitofrontal cortex on decision-making. Hyperactivity in these structures has been linked to obsessive compulsive disorder and, in line with the distinct functions of the different regions of OFC, we develop and test a novel hypothesis as to the psychological and neural bases of the obsessions and compulsions distinctive to that disorder.
Spinal Cord Injury Pain: Understanding Mechanisms To Develop Treatments
Funder
National Health and Medical Research Council
Funding Amount
$597,675.00
Summary
Spinal cord injury has devastating effects on health and quality of life. Many of the major consequences of injury, such as chronic pain and loss of voluntary voiding, are "invisible" – i.e., they are not as visible as limitations of mobility. Our study aims to define the neurobiological changes that cause development of persistent pain after spinal cord injury and use pharmacological tools to attenuate the development of pain.
Interactions Between Herpes Simplex Viral And Neuronal Motor Proteins
Funder
National Health and Medical Research Council
Funding Amount
$222,962.00
Summary
Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor p ....Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor protein which transports essential components down nerves from the spinal cord to the skin. Ultimately we aim to develop inhibitors of this process which might be candidates for further development as antivirals for control of recurrent herpes simplex.Read moreRead less
Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.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
Mapping the connectome that controls blood pressure. The connections that an individual brain cell receives from other cells ultimately determines its behaviour. Using a revolutionary new technique, the project will create a map of the brain cells that control blood pressure.
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
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
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
Discovery Early Career Researcher Award - Grant ID: DE120100992
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The role of neuropeptides driving plasticity in the control of blood pressure and breathing. This project aims to understand how pathways in the brain, that control blood pressure, develop 'memory' after repeated episodes of low oxygen, as occurs in sleep apnoea. Based on the assumption that long-lasting excitatory actions are responsible for this change in nerve behaviour this project will increase knowledge about how the brain controls blood pressure.