Dr Frances Edwards
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.
Normal and pathological aging of the retina
Patch clamp and imaging studies of fast synaptic transmission in the mammalian brain
In 1997 Frances Edwards and Maria Fitzgerald set up the MSc Neuroscience at UCL which Edwards then ran with a series of other colleagues until 2013. This is a highly academic research based degree exposing about 40 students per year to the most recent neuroscience research from across the whole of UCL in the form of research seminars, journal clubs and an extensive research project.
Now relieved of this major administrative and teaching load, Frances Edwards still contributes to the MSc and is teaching on a range of different undergraduate course in Neuroscience as well as contributing to the practical lab experience of undergraduate and graduate students.
Prof Stephen Perkins; Prof Shomi Bhattacharya; Prof Dave Shima; Prof Philip Luthert; Prof Dmitri Rusakov; Dr Imre Lengyel; Prof Fred Fitzke
- Shahab L, Plattner F, Irvine EE, Cummings DM, Edwards FA (2014). Dynamic range of GSK3α not GSK3β is essential for bidirectional synaptic plasticity at hippocampal CA3-CA1 synapses.. Hippocampus, 24(12), 1413 - 1416. doi:10.1002/hipo.22362
- Matarin M, Perona M, Salih D, Yasvoina M, Cummings D, Liu W, NahabooSolim M, Moens T, Paublete R, Ali S, Edwards F, Guelfi S, Hardy J, Latcham J, Fulleylove M, Richardson J, Desai R, Smith K (2014). A Genome-wide Gene-Expression Analysis and Database in Transgenic Mice during Development of Amyloid or Tau Pathology. Cell Reports, , - . doi:10.1016/j.celrep.2014.12.041
- Alfarez DN, De Simoni A, Velzing EH, Bracey E, Joels M, Edwards FA, Krugers HJ (2009). Corticosterone Reduces Dendritic Complexity in Developing Hippocampal CA1 Neurons. HIPPOCAMPUS, 19(9), 828 - 836. doi:10.1002/hipo.20566
- Donato R, Rodrigues RJ, Takahashi M, Tsai MC, Soto D, Miyagi K, Villafuertes RG, Cunha RA, Edwards FA (2008). GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx. Cell Calcium, 44(6), 521 - 532. doi:10.1016/j.ceca.2008.03.006
- Parsley SL, Pilgram SM, Soto F, Giese KP, Edwards FA (2007). Enriching the environment of αCaMKIIT286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP. Learning and Memory, 14(1), 75 - 83.
- Donato R, Miljan EA, Hines S, Aouabdi S, Pollock K, Patel S, Edwards F, Sinden J (2007). Differential development of neuronal physiological responsiveness in two human neural stem cell lines. BMC Neuroscience, 8, 36 - .
- De Simoni A, Edwards FA (2006). Pathway specificity of dendritic spine morphology in identified synapses onto rat hippocampal CA1 neurons in organotypic slices. Hippocampus, 16((12)), 1111 - 1124. doi:10.1002/hipo.20236
- Donato R, Page KM, Koch D, Nieto-Rostro M, Foucault I, Davies A, Wilkinson T, Rees M, Edwards FA, Dolphin AC (2006). The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression.. J Neurosci, 26(48), 12576 - 12586. doi:10.1523/JNEUROSCI.3080-06.2006
- Donato R, Rodrigues RJ, Cunha R, Edwards FA (2005). Purinergic control of GABA release.
- De Simoni A, Fernandes F, Edwards FA (2004). Spines and dendrites cannot be assumed to distribute dye evenly.. Trends in Neurosciences, 27(1), 15 - 16.
- Dean I, Robertson SJ, Edwards FA (2003). Serotonin drives a novel GABAergic synaptic current recorded in rat cerebellar Purkinje cells: a Lugaro cell to Purkinje cell synapse.. Journal of Neuroscience, 23(11), 4457 - 4469.
- De Simoni A, Griesinger CB, Edwards FA (2003). Development of rat CA1 neurones in acute versus organotypic slices: role of experience in synaptic morphology and activity.. The Journal of Physiology, 550(1), 135 - 147.
- Price GD, Robertson SJ, Edwards FA (2003). Long-term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus.. European Journal of Neuroscience, 17(4), 844 - 850.
- Price GD, Robertson SJ, Edwards FA (2003). Long-term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus. EUR J NEUROSCI, 17(4), 844 - 850. doi:10.1046/j.1460-9568.2003.02501.x
- De Simoni A, Griesinger CB, Edwards FA (2002). Correlation between morphology and spontaneous synaptic activity of CA1 neurones during development in acute and organotypic slices.
- Robertson SJ, Ennion SJ, Evans RJ, Edwards FA (2001). Synaptic P2X receptors. Current Opinion in Neurobiology, 11(3), 378 - 386.
- Dean I, Robertson SJ, Edwards FA (2000). Pharmacology of a novel synaptic current in rat cerebellar Purkinje cells.
- Price GD, Robertson SJ, Edwards FA (2000). UTP inhibits ATP and glutamate release in the rat medial habenula nucleus via a presynaptic mechanism.
- Robertson SJ, Price GD, Edwards FA (1999). P2X receptor-mediated synaptic currents in rat Purkinje cells.
- Nathanailides C, Griesinger CB, Caddy KWT, Edwards FA (1999). Computerised collection of electron microscopy data for analysis of synapses in rat hippocampal organotypic cultures.
- Edwards FA, Robertson SJ (1999). The function of A2 adenosine receptors in the mammalian brain: evidence for inhibition vs enhancement of voltage gated calcium channels and neurotransmitter release. Progress in Brain Research, 120, 265 - 273.
- Cooper EJ, Johnston GAR, Edwards FA (1999). Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices. The Journal of Physiology, 521, 437 - 449.
- Robertson SJ, Burnashev N, Edwards FA (1999). Ca2+ permeability and kinetics of glutamate receptors in rat medial habenula neurones: implications for purinergic transmission in this nucleus. The Journal of Physiology, 518(2), 539 - 549.
- Edwards FA (1998). Neuroscience - Dancing dendrites. NATURE, 394(6689), 129 - 130.
- Robertson SJ, Edwards FA (1998). ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine-mediated inhibition of release. The Journal of Physiology, 508, 691 - 701.
- Edwards FA (1998). Dancing dendrites, (News & Views). Nature, 394, 129 - 130.
- Robertson SJ, Edwards FA (1997). ATP is not a co-transmitter with glutamate at synapses of the medial habenula nucleus.
- Trommershaeusser J, Parthasarathy H, Edwards FA, Zippelius A (1997). Stochastic models of synaptic transmission in the CNS: importance of the diffusion constant and receptor distribution.
- Edwards FA, Robertson SJ, Gibb AJ (1997). Properties of ATP receptor-mediated synaptic transmission in the rat medial habenula. Neuropharmacology, 36, 1253 - 1268.
- Edwards FA, Gibb AJ, Colquhoun D (1992). ATP receptor-mediated synaptic currents in the central nervous system.. Nature, 359(6391), 144 - 147. doi:10.1038/359144a0
- HASLEHURST P, MESTRALLET C, GILBRIDE C, LAIMER C, CUMMINGS D, EDWARDS F (). Pushing the limits - using Imaris Filament Tracer to analyze dendritic spines.
- CUMMINGS D, RICHARDSON J, DAVIES C, EDWARDS F (). Early Synaptic Changes in Mouse Models of Alzheimer’s Disease.
- CUMMINGS D, SMITS H, JOEL Z, HANNAN T, LUGLI E, DAVIES C, DI DANIEL E, RICHARDSON J, EDWARDS F (). Early alterations in CA1 hippocampal synaptic transmission and morphology in the TASTPM mouse model of Alzheimer’s disease.
- CUMMINGS D, HANNAN T, RICHARDSON J, DAVIES C, EDWARDS F (). Early pathway-specific deficits in synaptic transmission in the TASTPM mouse model of Alzheimer’s disease.