Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe ....Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe how these connections are recruited during learning and memory, and then to test their function experimentally. The outcomes will extend the known neural circuitry that controls learning by defining how and where these unexplored pathways fit within it; thus advancing knowledge regarding neural regulation of behaviour.
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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.
The Missing Link: MGluR5 As A Therapeutic Target For Cognitive Decline In Dementia
Funder
National Health and Medical Research Council
Funding Amount
$563,622.00
Summary
Cognitive decline is a core feature of Alzheimer’s Disease (AD), yet there is no cure or treatment. Recent evidence suggests that a protein called mGluR5 could cause brain cells to lose function, leading to memory loss. This project will investigate whether disrupting mGluR5 function can improve cognition in mice with genetic AD. Memory will be assessed in mice using innovative touchscreen tests that closely mimic the tests used in humans.
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.
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.
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.
Alzheimer’s disease is a progressive brain disease which is results in memory loss and brain cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have previously developed a class of drugs that reverse memory loss targeting – these drugs target a protein called IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progressi ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and brain cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have previously developed a class of drugs that reverse memory loss targeting – these drugs target a protein called IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progression of Alzheimer’s disease pathology.Read moreRead less
Mechanisms And Consequences Of Cholinergic Signaling In Neocortical Pyramidal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that ac ....Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that acetylcholine produces opposing phasic and tonic actions on the excitability of brain cells in the cortex. The data collected in this study will reveal the receptor type, intracellular signalling pathways, and ionic mechanisms through which acetylcholine influences information processing in the brain. Together, these results will provide a framework for understanding the biological basis by which acetylcholine influences cognitive function. This new knowledge will in turn increase our understanding of why dysfunction of this important neurotransmitter system leads to the functional deficits observed in Alzheimer s Disease and other forms of dementia, and will hopefully suggest new targets for therapeutic intervention.Read moreRead less
Defining Reciprocal Neural Circuits That Regulate Appetite And Memory
Funder
National Health and Medical Research Council
Funding Amount
$341,935.00
Summary
How we remember meals influences how much we eat at later time points. This kind of memory likely comes from both the traditional brain areas associated with memory formation, and from areas associated with regulating appetite. How these two brain regions work together to help animals remember what they ate, where they found it, and whether they liked it is not known. This project investigates how these memories are formed and how they are used by animals to make decisions about future meals.
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