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.
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.
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.
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.
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.
Excitability And Hyperexcitability Of Neural Circuits In The Rodent Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$371,807.00
Summary
We are studying the properties of neurons (nerve cells) and brain circuits that enable mammals to recognise and remember odours. Our experiments will focus on neurons in the odour-processing region of the cerebral cortex of mice. This work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the external world. Our findings will also provide a deeper understanding of the causes of epilepsy, leading to improved treatments.
Absence epilepsy is the commonest form of idiopathic generalized epilepsy. It can lead to hundreds of seizures per day, and mainly affects children between the ages of four and eight. Its cause is in most cases unknown. In this study we will use a rat model of absence epilepsy to investigate the cellular basis of this disease. Preliminary work indicates that a particular protein - HCN1 - is reduced in the cortex of rats with absence epilepsy. This protein codes for a pore in the membrane of nerv ....Absence epilepsy is the commonest form of idiopathic generalized epilepsy. It can lead to hundreds of seizures per day, and mainly affects children between the ages of four and eight. Its cause is in most cases unknown. In this study we will use a rat model of absence epilepsy to investigate the cellular basis of this disease. Preliminary work indicates that a particular protein - HCN1 - is reduced in the cortex of rats with absence epilepsy. This protein codes for a pore in the membrane of nerve cells, which acts like a switch. We have preliminary evidence that in rats with absence epilepsy this switch does not work properly. We wish to investigate how this influences the activity of nerve cells in rats with absence epilepsy. Furthermore, as absence epilepsy is an inherited disease, we wish to track down the genetic basis of this disease. This will give us clues as to the cause of the disease in this rat model. This research will shed light on the potentially important role of the HCN1 protein in absence epilepsy, which may represent an potentially new therapeutic target for the development of drugs for the treatment of absence epilepsy.Read moreRead less
The Neuronal PIKfyve Complex Regulates Neurotransmission And Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Neuronal communication is essential for the functioning of our bodies and mind. We have identified a novel pathway for the regulation of this process involving a little studied lipid, PI3,5P2. This lipid also appears to be important for neuronal survival. We will investigate the regulation and function of this lipid in neurons. The outcomes of this proposal will be an important step closer to understanding the processes underlying neuronal communication and neurodegeneration.
The neocortex is the region of the brain that underlies all cognitive functions. Mental disorders, such as schizophrenia, occur when the communication between nerve cells in the neocortex breaks down. We propose to make electrical measurements from the thin processes of neurons that receive input from widely separated neocortical areas to understand how areas of the neocortex are functionally interlinked, with the ultimate aim to identify how these processes are disturbed in mental disorders.
Molecular Mechanisms And Pharmacology Of The Dynamins
Funder
National Health and Medical Research Council
Funding Amount
$883,375.00
Summary
His research focuses on the molecular mechanisms of synaptic transmission in the nervous system to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. There are three dynamin genes: dynI, II and III with diverse functions in the different parts of the body.