How are memories stored in the brain? We know much about the brain regions involved in memory storage but we know little or nothing about how individual memories are represented and stored within those brain areas. The purpose of this project is to label and manipulate the specific subsets of brain cells that store individual memories. We will label memory-bearing cells in multiple brain regions and then ask how the connections between those cells encode learned information in the brain.
Development Of Small Molecule IRAP Inhibitors For Treating Memory Deficits
Funder
National Health and Medical Research Council
Funding Amount
$369,898.00
Summary
We have identified a series of small molecule compounds based on their ability to inhibit the catalytic activity of a protein, IRAP using a computer model of IRAP to screen chemical libraries. This research proposal aims to investigate the properties of these compounds and their ability to treat Alzheimer's dementia. At the conclusion of this project, we will have 2 families of lead compounds suitable for development into a new class of therapeutic agents for treating Alzheimer's disease.
Development Of Small Molecule Inhibitors Of IRAP - Potential Use For The Treatment Of Memory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$195,450.00
Summary
This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusio ....This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusion of this project, we will have elucidated important information on the specificity of the memory effects and the structure activity relationship of this family of compounds. We will have identified and characterised a lead compound for development into a new class of cognitive enhancers.Read moreRead less
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
IRAP inhibitors are currently being developed as a new class of drugs for treating dementia and other forms of memory deficits. However, there are still gaps in our knowledge about how these drugs act to improve memory. The experiments outlined in this proposal will provide important insights into the drug action in different mouse models of memory deficit.
Transient Receptor Potential Channels, Calcium And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$410,284.00
Summary
This research outlined in this application aims to uncover the molecular mechanisms that cause Alzheimer's disease (AD). Specifically the research will examine the mechanism by which Abeta, a protein which plays a central role in AD, causes neurodegeneration. The significance of this work is that it may help to identify new targets for AD drug development.
Cracking The Epigenetic Code: Understanding The Mechanisms Of Memory Associated With Anxiety-related Disorders And Their Treatment
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
The primary goal of my research programme is to elucidate how the epigenome coordinates experience-dependent gene expression underlying associative learning and memory using paradigms relevant for understanding fear-related anxiety disorders. My research on DNA modifications and newly emerging findings in the realm of RNA biology is changing the way we think about gene-environment interactions, the broader impact of which will most certainly continue to be felt for years to come.
Neural Correlates Of Fear Conditioning And Extinction
Funder
National Health and Medical Research Council
Funding Amount
$901,899.00
Summary
The amygdala is a part of the brain that processes emotional information. Disorders of amygdala function lead to a host of anxiety-related disorders such as phobias and post-traumatic stress disorder. In this grant we will study how the amygdala processes sensory information from the environment and forms memories of salient events. These findings will tell us how memories are formed, stored and retrieved. In the long term it will provide targets for the development of new anxiolytic agents
BDNF Genotype And Emotional Memory In Post-traumatic Stress Disorder
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
This project addresses the question of why some people develop PTSD following trauma and others don’t. It will assess the influence of genetics (specifically a genotype that influences Brain Derived Neurotrophic Factor) on emotional memory processes as distressing emotional memories are a core symptom of PTSD. If we find that people with a particular genetic profile have a greater risk of developing intrusive memories after trauma, this will help us better target treatment for those individuals.
Enzymes that generate or degrade peptides serve important roles - alterations in their activity can impact on a diverse range of physiological processes in healthy and diseased states. Angiotensin is a peptide that plays a critical role in regulating blood pressure and fluid balance - drugs that block the activity of its processing enzymes forms an important class of medication used to treat hypertension and heart disease. My research interest is in discovering novel roles for these enzymes.