Investigation Of The Molecular Mechanisms Underlying Alpha Synuclein Function At The Presynapse
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Parkinson’s Disease (PD) is a common brain disease affecting 7 million people worldwide. It is caused by the death of brain cells. ?-synuclein is a protein in that brain that is likely to contribute to the cell death in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand how normal brain processes are affected in diseases such as PD.
Sulfonadyn-based Dynamin I-specific Inhibitors And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$835,291.00
Summary
Epilepsy affects 1% of people, yet 30% do not respond to anti-epileptic drugs (AEDs). Traditional drug discovery fails to improve this situation. Our team discovered dynamin as a new target for better AED design and our lead sulphonadyns reduces seizures in animals. We will design better sulfonadyns that can ultimately be used for clinical trials by designing the drugs away from its actions outside of neurons. If successful, this will accelerate new AED development with less side-effects.
Impact Of Somatic Versus Dendritic Inhibition On Neuronal Output
Funder
National Health and Medical Research Council
Funding Amount
$1,047,686.00
Summary
The brain is made up of literally billions of neurons connected in complex networks. These neurons come in two primary flavors - excitatory and inhibitory - which work in balance. Too much excitation and the brain becomes epileptic, too much inhibitory and we go into a coma. This proposal focuses on the role of specific inhibitory cell types in regulating brain function, and has relevant to a range of neurological disorders from epilepsy, to schizophrenia to depression.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
Targeting The Synaptic Actin Cytoskeleton In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$840,741.00
Summary
Dementias have become one of the fastest growing sources of major disease burdens in developed countries with about one in fifteen Australians older than 65 being affected. We will study how pathological stimuli disrupt nerve cell connections in the brain by impacting on the cellular architecture at these connections. Findings from our study will provide profound new insights in how nerve cells communicate with each other and how this communication is breaking down in disease.
Learning And Network Plasticity In A Primitive Sensory Cortex
Funder
National Health and Medical Research Council
Funding Amount
$461,557.00
Summary
Our brain is a uniquely powerful supercomputer, in part because it is ‘plastic’ -- that is, it can change itself when we adapt or learn something new. An understanding of the causes of brain plasticity is an essential part of any quest to understand the brain in sickness and in health. This research uses a laser microscope to ‘read the minds’ of mice as they learn about odours. By observing plasticity in action, we will gain deeper insights into normal brain function.
Persistent Firing In Cortical Interneurons: Mechanisms And Potential Anticonvulsant Role
Funder
National Health and Medical Research Council
Funding Amount
$520,552.00
Summary
The normal brain treads a fine line between too much electrical activity (epilepsy) and too little (sedation). We have discovered a class of brain cell that seems to behave like a sentinel, monitoring brain activity for signs of epilepsy. If a seizure occurs, this cell switches on an electrical brake that dampens excess activity. In this project we will study how this brake works and whether it really can inhibit seizures. Our research may lead to better treatments for epilepsy.
The Functional Interplay Between Alpha Synuclein And Synaptophysin In Synaptic Vesicle Recycling
Funder
National Health and Medical Research Council
Funding Amount
$405,461.00
Summary
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder, affecting 7 million people worldwide. ?-synuclein is a protein in that brain that is likely to contribute to the death of brain cells in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand the processes that go awry in neurodegenerative disease states such as PD.
Neural Circuits For Odour-processing In The Rodent Piriform Cortex 'in Vivo'
Funder
National Health and Medical Research Council
Funding Amount
$488,817.00
Summary
We are studying the brain circuits that enable mammals to recognise odours. We will apply puffs of odorants to the nose of an anaesthetised mouse while measuring electrical signals in the odour-processing region of its cerebral cortex. Our work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the world. This is basic research that will, in the longer term, shed light on the disturbances that occur during mental illness.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.