Unravelling A New Fatty Acid Pathway Involved In Neuroexocytosis And Memory
Funder
National Health and Medical Research Council
Funding Amount
$539,631.00
Summary
This proposal build on the establishment by our laboratory of the assay capable of detecting free fatty acids, with great accuracy and sensitivity. Using this assay we have uncovered a completely new pathway highlighting the production of saturated free fatty acids linked to learning and memory. We will fully define how this pathway is regulated in the brain.
A core feature of clinical anxiety is the inability to learn about safety and suppress fear. Impaired safety learning underpins excessive fear responding, overgeneralisation of fear, as well as treatment resistance in clinical anxiety. Very little is known about the brain mechanisms for learned safety. This project maps and manipulates these mechanisms to lay the basic science foundation for the next generation of treatments of anxiety.
Disorder in the circuits that process emotional stimuli are central in the pathogenesis of anxiety disorders. In this grant we will study the circuits that are inolved in fear learnng. Our results will provide the background to developing more effective therapies for a range of anxiety related disorders such as generalised anxiety and post traumatic stress disorder.
Fear Relapse: Neural Substrates Underlying Its Inhibition And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$437,476.00
Summary
Exposure-based therapies are effective for anxiety disorders such as post traumatic stress, but two challenges remain: 1) patients that have learned to inhibit their fear are likely to relapse, requiring further therapy; 2) many drop out of therapy since it is aversive and anxiety provoking. We use an animal model to: 1) identify the neural substrates underlying fear inhibition; and 2) determine the conditions that prevent relapse and encourage participation in treatment.
While we need to consume salt, too much can be harmful and is in fact directly linked to ~5% of deaths annually in Australia. We have identified a system in the brain that regulates salt intake. Going forwards we will fully elucidate the pathway(s) implicated in regulation of salt intake, thereby identifying strategies to reduce excessive salt consumption.
The Effect Of Oxytocin On The Formation, Expression And Inhibition Of Fear Memories
Funder
National Health and Medical Research Council
Funding Amount
$390,243.00
Summary
Oxytocin is a hormone peptide which reduces amygdala activation to threatening stimuli and reduces anxiety in people and laboratory rodents. These results suggest that oxytocin could be a valuable pharmacological adjunct to exposure-based therapy for anxiety disorders. However, several questions must be answered before its therapeutic potential can be determined. As such, this project examines the effects of oxytocin on fear-related behaviours in rats, and neural fear circuits in the amygdala.
The amygdala is a region of the brain involved in assinging emotional salience to our sensory world. Disorders of amygdala function lead to a range of anxiety related disorders. In this grant we aim to understand the neural circuits that are invovled in one form of learning that engages the amygdala - fear conditioning.
This project maps and manipulates the brainstem mechanisms causing expression of fear. It does so using brain cell type and brain circuit specific mechanisms.
Modelling Post-traumatic Stress Disorder In Rats: Hypervigilance And Spread Of Fear
Funder
National Health and Medical Research Council
Funding Amount
$353,248.00
Summary
Post-traumatic stress disorder is characterized by hypervigilance and spread of fear across a network of trauma related memories. The consequences of hypervigilance for information processing, and the mechanisms involved in the spread of fear, are unknown. This project uses animal models to identify these consequences and mechanisms, and their substrates in the brain. It examines how a network of trauma related memories can be erased, and thus, how core symptoms of the disorder may be treated.
Debilitating anxiety disorders, such as post-traumatic stress disorder or panic disorder, affect 14% of adult Australians and current therapy is often ineffective. The amygdala is a brain region that is key to learning fear responses but also in reducing our fear responses. This project will determine whether the brain’s own endogenous opioids can modify the activity of the amygdala in order to provide new leads for novel pharmacotherapies with enhanced efficacy.