The Role Of Stargazin And TARP Phosphorylation In Synaptic Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$423,305.00
Summary
A constant change in the strength of synaptic communication between neurons is critical for higher brain functions such as learning and memory. Synaptic strength is determined in part by the number of receptor ion channels at the synapse. This project will characterise how key interacting proteins regulate the synaptic targeting of these receptors in vivo. This research aims to understand the mechanisms of synaptic plasticity that may ultimately lead to new therapies for various brain disorders.
Mechanisms Of Glutamate Receptor Maturation In Chicken Brain
Funder
National Health and Medical Research Council
Funding Amount
$418,980.00
Summary
In the brain, many key proteins involved in signalling change during development as part of the fine tuning of the network of connections between nerve cells. Disorders of this fine tuning are thought to result in a number of neurological or psychiatric conditions such as epilepsy and schizophrenia. This project will investigate the maturation of signalling molecules in the brain (receptors for the neurotransmitter glutamate, key enzymes called protein kinases and protein phosphatases that contr ....In the brain, many key proteins involved in signalling change during development as part of the fine tuning of the network of connections between nerve cells. Disorders of this fine tuning are thought to result in a number of neurological or psychiatric conditions such as epilepsy and schizophrenia. This project will investigate the maturation of signalling molecules in the brain (receptors for the neurotransmitter glutamate, key enzymes called protein kinases and protein phosphatases that control the activity of receptors and scaffolding proteins that bind the whole lot into a signalling complex). The project uses chickens as a novel animal model because chicken brain has a slow maturation that occurs well after the initial wiring of the brain is complete. This enables the maturation changes to be clearly identified and experimentally modified. The project combines investigations at the molecular, physiological and behavioural levels. The effects of hormones and drugs on maturation will be investigated. Because brain maturation in humans is also slow an understanding of the way in which this maturation is controlled may provide insights into what causes some neurological-psychiatric disorders in children and adolescents and how to treat or prevent them.Read moreRead less
The Cystine Glutamate Antiporter And Classical Glutamate Transporters In Normal And Pathological Brains And Retinae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction ....This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction of action and release glutamate. The current study investigates a transport system (called the cystine-glutamate antiporter) where the normal direction of action is to release glutamate. This system has been overlooked despite evidence that it could be involved in releasing glutamate and thus contribute to the death of nerve cells in a variety of human pathologies including glaucoma of the eye, epilepsy, and brain damage that occurs when the blood supply to the brain is interrupted, such as after a heart attack. This study examines both human tissues and animal models of disease states to determine if similar transport systems are present and if the cystine-glutamate antiporter might contribute to human nervous diseases. The function and distribution of the cystine-glutamate antiporter will be compared with classical transporters, under normal and pathological conditions, including situations where we have shown that it is possible to experimentally perturb normal glutamate transporter expression.Read moreRead less