The Extinction Of Conditioned Fear And Its Implications For Cue Exposure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$322,430.00
Summary
This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavl ....This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavlovian conditioning, subjects (typically rats) are exposed to a signaling relation between an initially neutral stimulus (e.g., a noise) and a feared outcome (e.g., foot shock). When later repeatedly exposed to the initially neutral but now feared stimulus (the noise) in the absence of the feared outcome, the fear reactions it acquired progressively decline until eventually it fails to elicit any such reactions. The fear reactions are said to have been extinguished. There has been significant progress in understanding the psychological processes and neural mechanisms underlying the acquisition of fear reactions, but much less is known about the processes and mechanisms underlying the extinction of these reactions. The project has two general objectives. The first is to determine the conditions of extinction training that promote long-term loss of fear reactions. The second objective is to determine how the brain controls this extinction of learned fear. Achieving these aims will be significant for two reasons. First, it will contribute to understanding the mechanisms by which animals (including people) learn to adjust their behaviour to bring it into line with the current relations that exist between events in the world. Second, it will provide important information about how such adjustment is facilitated or impaired across extinction training and, thereby, contribute towards understanding both the successes and failures of cue exposure therapy for fear-related disorders.Read moreRead less
Cognitive Enhancement In Schizophrenia Via Selective Oestrogen Receptor Modulator.
Funder
National Health and Medical Research Council
Funding Amount
$396,380.00
Summary
Cognitive dysfunction in schizophrenia is resistant to treatment and related to poor community functioning and quality of life. In spite of the widely appreciated magnitude of the problem, there is still a critical gap in our knowledge concerning treatments to reverse these cognitive deficits. The proposed research is significant because it will clarify the role of hormones and genes in relation to cognitive deficits in schizophrenia and it may help patients improve their level of functioning.
Investigating The Role Of The UPF3B Gene And Nonsense Mediated RNA Decay (NMD) Process In Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$572,710.00
Summary
Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes c ....Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes causing various forms of intellectual disability. Surprisingly the number of genes, in which mutations cause various forms of intellectual disability is unexpectedly high. Just on the human X-chromosome we expect in excess of 200 such genes, which is nearly 30% of the gene content of this chromosome. We propose to study a novel gene, UPF3B, we recently identified to be mutated in a form of intellectual disability. The normal function of this gene and its protein is known to a certain extent. The UPF3B protein plays a role of a guardian of other genes in human (and also other species) cells. The role of the UPF3B protein is to prevent erroneous genetic information to be used for the building of proteins with potentially toxic effects to the organism. In our patients this process clearly malfunctions as a consequence of the damaged UPF3B gene. We propose to shed some more light in to the molecular intricacies of this process with the aim to better understand the mechanics of the process. Families, which participate in our studies and have this gene involved will benefit from the availability of direct test. Multiple other families around the world are also likely to benefit, now or in the future.Read moreRead less
Relaxin-3 Systems In Brain: Validation Of Neural Targets And Functional Roles
Funder
National Health and Medical Research Council
Funding Amount
$537,579.00
Summary
Our laboratory recently discovered the brain 'transmitter' called 'relaxin-3', and are researching how it affects brain activity and animal physiology and behaviour. Findings suggest that relaxin-3 can modulate memory, responses to stress and other complex behaviours. Identifying the various actions of relaxin-3 in the brain could provide potential new treatments for conditions such as anxiety-depression, cognitive deficits (dementia) and schizophrenia.