Address429 Anatomy Bldg
Dept Neuroscience Physiology Pharmacology
Professor of Neurodegeneration
Neuro, Physiology & Pharmacology
Div of Biosciences
The hippocampus in health and disease; Alzheimer's disease: how synaptic transmission goes wrong, long before you can detect cognitive deficits
Memory must involve activity-dependent changes in the network of communication between brain cells. The hippocampus has long been known to be involved in the laying down of memory and much work on this field has concentrated on this area of the brain. Cellular phenomena have been described by which the communication at individual synapses, (the connections between individual neurones), can be strengthened, ('long-term potentiation', LTP) or weakened ('long-term depression', LTD).
In the Edwards lab we are interested in how synapses change and how they react to each other in both health and disease.
1. How synapses work and change in the healthy brain: In healthy mouse and rat brains we use high resolution recording techniques to measure the electrical communication between brain cells in acute and organic brain slices. In addition we can image these cells in detail and observe the changes that occur as connections strengthen and weaken both in response to incoming activity but also in response to changes in neighbouring connections. Understanding such subtle mechanisms is essential to understanding how the healthy network develops and is maintained in terms of general day to day function and the laying down and retrieval of memory. It is also these functions which are likely to go wrong in many neurodegenerative diseases.
2. What goes wrong in Alzheimer's disease: So far there has been no success in treating Alzheimer's disease. Although some drugs temporarily help the symptoms in some people, nothing has been discovered to slow or reverse the progression of the disease. Considering the massive scale of this disease and the devastating effects on the sufferers as well as their families, not to mention the economy, this is an urgent problem to address. Working on the hypothesis that the past failure is because the attempts at treatment come too late, once the brain is already too damaged for repair, we are both studying the earliest changes that occur and the middle period; a long window of opportunity as plaques develop but irreversible damage is yet to occur.
Using mice which express human genes with mutations known to occur in Alzheimer's disease and other disease states, we have observed substantial changes in synaptic transmission at very early stages. By understanding these changes we aim to develop new therapies in an attempt to stop the progression of the disease before substantial irreversible damage has occurred.
The work has now expanded to investigate the genome-wide gene expression in these mice revealing initial changes in synaptic genes followed by a very tight correlation between plaque development and immune genes. Later loss of synaptic genes, presumably indicated to loss of synapses and neurodegeneration is more closely linked to neurofibrillary tangles. Ongoing studies involve the manipulation of the genes of interest to understand which genes influence the susceptibility of the brain to the formation of neurofibrillary tangles and neurodegeneration.
|Australian National University|
Master of Science
|University of Sydney|
Bachelor of Science (Honours)
|University of Sydney|
After staying on as a postdoctoral fellow in Sakmann's lab, in 1990 she joined David Colquhoun’s group in Pharmacology at UCL as a Wellcome European Fellow.
After returning to Australia in 1992 Frances held a Queen Elizabeth II Research Fellowship at the University of Sydney from 1993 until 1996.
In 1996 she joined the Department of Physiology at UCL. Until 2010 the focus of the Edwards lab was mechanisms of fast synaptic transmission and the role of dendritic spines in plasticity using electrophysiology and confocal imaging.
In 2010 the research direction largely shifted to research on Alzheimer's disease, studying several transgenic mouse models of human mutations in the amyloid pathway or microtubule-associated protein tau.
The approaches have expanded to include a range of molecular biology and immunohistochemical techniques and genetics (in collaboration with John Hardy).
Along with synaptic changes the lab is now interested in the role of the immune system in Alzheimer and the interface between amyloid plaques and neurofibrillary tangles.