A Window Of Vulnerability: Impaired Fear Inhibition In Adolescent Rats
Funder
National Health and Medical Research Council
Funding Amount
$335,849.00
Summary
Adolescence is a period of increased vulnerability to anxiety disorders. The brain undergoes substantial maturation during adolescence, particularly the prefrontal cortex (PFC), a region critical for inhibiting fear. This project examines why fear inhibition is impaired in adolescents and compares the neural mechanisms mediating treatments that enhance fear reduction in adolescence. This research adds new knowledge about novel approaches for early interventions for adolescent anxiety.
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.
Developmental Differences In The Role Of The Medial Prefrontal Cortex In Fear Regulation
Funder
National Health and Medical Research Council
Funding Amount
$354,481.00
Summary
This project explores the neural circuitry involved in fear expression early in life, and how early life experiences can affect this circuitry. A better understanding of the neural circuitry underlying fear regulation across development is essential given that the majority of anxiety disorders first appear in childhood or early adolescence.
Exploring DNA Methylation As A Mechanism For Long-term Memory For Fear Extinction
Funder
National Health and Medical Research Council
Funding Amount
$415,322.00
Summary
Traumatic experiences are well remembered. In some cases, fear-related memories become debilitating and require therapeutic intervention to diminish the impact of these kinds of memories on daily living. Such therapies engage a process of inhibitory learning called fear extinction. Since anxiety disorders are particularly sensitive to relapse even after extensive exposure therapy, a deeper understanding of the extinction process is crucial if we are to develop more effective treatment protocols ....Traumatic experiences are well remembered. In some cases, fear-related memories become debilitating and require therapeutic intervention to diminish the impact of these kinds of memories on daily living. Such therapies engage a process of inhibitory learning called fear extinction. Since anxiety disorders are particularly sensitive to relapse even after extensive exposure therapy, a deeper understanding of the extinction process is crucial if we are to develop more effective treatment protocols for a variety of anxiety disorders.Read moreRead less
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.
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.
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.
Anxiety and addiction are disorders with high co-morbidity that present a major worldwide public health concern. Treatment in both cases often involves an approach called extinction which helps to reduce the relapsing nature of these disorders. This grant is designed to examine the role of a specific protein in addiction and anxiety, by virtue of its involvement in the process of extinction.