The Role Of Presynaptic Inhibition In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$466,045.00
Summary
Inhibitory nerve cells in the spinal cord are thought to play an important role in governing the interaction between painful and non-painful stimuli. Defects in this process underlie allodynia, an important symptom of neuropathic pain. We will use recent advances in genetic techniques (optogenetics) to manipulate and study how inhibitory nerve cells separate touch and pain signalling in the spinal cord of normal and neuropathic animals.
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
A DENDRITIC SUBSTRATE FOR THE CHOLINERGIC CONTROL OF NEOCORTICAL OUTPUT
Funder
National Health and Medical Research Council
Funding Amount
$898,340.00
Summary
The forebrain cholinergic system controls neocortical activity and cognitive function. This project will investigate the mechanisms by which the cholinergic system controls neocortical circuit activity in rodent models using advanced optical and electrical recording methods. The results will provide a foundation for the understanding of how dysfunction of the cholinergic system results in cognitive decline in humans, and identify new targets for improved treatment of human cognitive impairment.
Cognitive Inflexibility And The Development Of Pathological Habits In Brain Diseases
Funder
National Health and Medical Research Council
Funding Amount
$883,946.00
Summary
Pathological habits are observed in severe mental health conditions including dementia, obsessive-compulsive disorder (OCD), schizophrenia, depression and addiction. This application aims to provide the mechanistic detail required for therapeutic targeting to restore flexible decision making in these conditions.
Protecting Synaptic Connectivity In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$573,573.00
Summary
In Alzheimer’s disease, connections between neurons (synapses) are progressively damaged. The BACE inhibitor class of drugs entering Phase III clinical trials may slow the pace of neurodegeneration in patients with dementia. However, these drugs may simultaneously have negative effects on synapse function, learning and memory. This study will assess the effect of BACE inhibition on synapse properties and cognition and identify the contribution of key proteins affected by this treatment.
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.
A Potential Analgesic Target In A Novel Clinically-relevant Neuropathic Pain Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$685,811.00
Summary
Persistent pain arising from tissue damage, to nerves, muscles or joints for example, is devastating for patients and a huge social and economic burden. This work will investigate one of the pathways that goes awry after sensory nerves are damaged. These experiments will also test whether a drug being developed to treat Alzheimer's disease is effective at blocking the persistent nerve hypersensitivity that sometimes develops after injury.
Does IRAP Contribute To Alzheimer's Disease Pathology?
Funder
National Health and Medical Research Council
Funding Amount
$743,042.00
Summary
Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, 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 pro ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, 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
Standardisation Of Prepulse Inhibition Of The Startle Reflex For Pharmacological And Interspecies Comparisons
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differe ....People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differences in ski slopes as well. The size of the startle reflex can also be reduced by preceding the startling sound with a quiet stimulus a few tens of milliseconds before the startling stimulus. This is known as prepulse inhibition of the startle reflex or PPI for short. There is much interest in PPI, because it differs in people with certain mental illnesses, such as schizophrenia or post-traumatic stress disorder, and certain neurological illnesses, such as Huntington's chorea. It is also affected by drugs, including stimulants, stress hormones, and cannabis. In almost all the hundreds of experiments on PPI the effect of the prepulse on the response to a startling stimulus is measured at only one startling stimulus loudness. This loudness can be at very different parts of the ski slope for different people or other animals: it may be in the steep slope for one person, well into the plateau for another, or even at the bottom of the ski slope below the threshold in others. The effect of PPI is very different depending on what part of the ski slope the loudness represents. A lack of consistent effects in the literature on PPI by drugs and genetics is explained by this difference. Experiments are planned that will investigate the effect of drugs that are similar to those that treat schizophrenia, stress hormones and cannabis on the effect of prepulses on the whole ski slope. This procedure will provide the consistency in results so far absent.Read moreRead less