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.
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.
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.
The Role Of Neuronal Hyperactivity And Neurotrophic Factor Signalling In Synaptogenesis, Dendrogenesis And Neuron Death In Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,331.00
Summary
Using mice with mutant genes causing amyotrophic lateral sclerosis, we will test whether motor neuron hyper-excitability during early development causes excessive synapse and dendrite formation, ultimately leading to neuronal death. We will also test whether activity-dependent secretion of neurotrophic factors and activation of their receptors plays a role in this disease. This will show whether neuronal hyper-activity and neurotrophic factor signaling plays a causal role in this disease.
Excitatory Synaptic Circuitry And Plasticity In The Amygdala.
Funder
National Health and Medical Research Council
Funding Amount
$405,750.00
Summary
The amygdala is a key structure in the neuronal circuitry that underlies the analysis of emotional information. In particular this structure plays a major role in the processing of fear-related information. Disorders of the processing and storage of such information are thought to be the major underlying cause of mental disorders such as panic attacks, anxiety and post traumatic stress disorder. Understanding the physiology of this structure and the ways in which this can change in response to v ....The amygdala is a key structure in the neuronal circuitry that underlies the analysis of emotional information. In particular this structure plays a major role in the processing of fear-related information. Disorders of the processing and storage of such information are thought to be the major underlying cause of mental disorders such as panic attacks, anxiety and post traumatic stress disorder. Understanding the physiology of this structure and the ways in which this can change in response to various stimuli is necessary for the development of rational therapies that target the amygdala.Read moreRead less
The corticospinal pathway is the major route from the brain to the spinal cord for the control of voluntary movement in people. Little is known about how transmission through this pathway might alter with activity. It is known that, elsewhere in the brain, connections between nerve cells can be made stronger or weaker by specific patterns of activity and it is thought that such changes underlie learning and memory. We propose that similar changes might happen in the spinal cord at the connection ....The corticospinal pathway is the major route from the brain to the spinal cord for the control of voluntary movement in people. Little is known about how transmission through this pathway might alter with activity. It is known that, elsewhere in the brain, connections between nerve cells can be made stronger or weaker by specific patterns of activity and it is thought that such changes underlie learning and memory. We propose that similar changes might happen in the spinal cord at the connection between the nerve cells which carry signals from the brain and the nerve cells which carry the signals out to the muscle. This project will demonstrate that the connections in the pathway from the brain to the muscle can be strengthened or weakened in a controlled way by imposed patterns of activity. In addition, we know that after voluntary contractions, there are dramatic changes in the way signals in this pathway are transmitted to muscles. After brief strong voluntary contractions, muscle responses are immediately reduced. After longer contractions in which the muscles become fatigued, the reduction is followed by an increase in responses which can last many minutes. Thus, this project will also study changes in the pathway from the brain to the muscle after natural activity. The effects of changes induced by artificial or natural activity on the control of voluntary movement will also be investigated. Understanding how activity drives changes in the pathway that controls voluntary movement is important for all situations that involve learning motor tasks. These include normal development and learning of motor skills, as well as rehabilitation after all kinds of nerve or muscle injury. It is also important in understanding motor changes that occur when activity is altered by disorders like spinal cord injury or stroke. Improved understanding of the processes occuring should allow improvement in rehabilitation therapies.Read moreRead less
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
The Role Of Action Potentials In Local Calcium Signalling And Induction Of Different Forms Of LTP
Funder
National Health and Medical Research Council
Funding Amount
$330,691.00
Summary
Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and ....Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and memory. These forms of LTP have different persistence characteristics - LTP 1 is relatively short-lasting, LTP 2 is of intermediate duration, and LTP 3 is very long-lasting and perhaps even permanent. Each form of LTP is selectively triggered by an increase in calcium in a different part of the neuron. In the present study, I will investigate the relationships between electrical activity in different parts of the neuron in order to define the 'rules' for triggering each form of LTP. This information is important for future studies into the specific role played by each form of LTP in learning and memory processing in the brain. A better understanding of the relationship between LTP and learning and memory will assist in developing effective treatment strategies for disorders of memory, including Alzheimer s disease, addictive bahaviour, and learning disorders.Read moreRead less