Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
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.
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 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.
Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Stimulus Induced Synaptic Plasticity In The Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$428,777.00
Summary
Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating ....Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating doses required for adequate pain relief and the limited efficacy of current drug therapies in some clinically important pains states. The persistence of pain after the original injury has resolved suggest the development of adaptations that result in the ongoing pain. The changes in neurobiology underlying persistent pain are poorly defined. A better understanding of this neurobiology will result in better therapeutic approaches to persistent pain. The amygdala is a brain region that is important for pain processing, endogenous analgesia and emotion. A neuronal pathway that delivers information about pain to the amygdala has recently been shown to be critical for the development of persistent pain. Little is known about whether this critical neuronal pathway is modified by pain. This project will determine using electrical and chemical techniques how a brief or persistent painful stimulus changes the delivery of painful information to the neurons in the amygdala. The changes produced by a brief painful stimulus likely represent the initial changes in the development of a persistent pain state. This information may allow us to more fully understand the transition from acute to persistent pain and the changes defined may be sensitive to pharmacological modulation. Preventing or inhibiting these pain induced changes may provide better treatment for persistent pain or ideally prevent people undergoing the transition from acute to persistent pain.Read moreRead less
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.