Dr Frances Edwards
Processing of Memory; Plasticity and Homeostasis in the healthy hippocampus; 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 collaborating to develop early detection systems so that these early changes could be targetted with new therapies.
Using mice which have human 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. We are also collaborating with Professor Francesca Cordeiro and Dr Li Guo at the Institute of Opthalmology to develop early detection systems using the retina as a window on the brain.
Normal and pathological aging of the retina
Patch clamp and imaging studies of fast synaptic transmission in the mammalian brain
Frances Edwards runs the MSc Neuroscience UCL together with Drs Stephen Price (CBD) and Robin Hayman (Psychology). 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. These students almost all go on to do PhDs many feeding into UCL PhD programmes.
Prof Stephen Perkins; Prof Shomi Bhattacharya; Prof Dave Shima; Prof Philip Luthert; Prof Dmitri Rusakov; Dr Imre Lengyel; Prof Fred Fitzke
- 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.
- 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 (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.
- 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.
- Nathanailides C, Griesinger CB, Caddy KWT, Edwards FA (1999). Computerised collection of electron microscopy data for analysis of synapses in rat hippocampal organotypic cultures.
- 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, 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.
- Robertson SJ, Price GD, Edwards FA (1999). P2X receptor-mediated synaptic currents in rat Purkinje cells.
- 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.
- 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.
- Robertson SJ, Edwards FA (1997). ATP is not a co-transmitter with glutamate at synapses of the medial habenula nucleus.
- 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
- 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, RICHARDSON J, DAVIES C, EDWARDS F (). Early Synaptic Changes in Mouse Models of Alzheimer’s Disease.
- 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, HANNAN T, RICHARDSON J, DAVIES C, EDWARDS F (). Early pathway-specific deficits in synaptic transmission in the TASTPM mouse model of Alzheimer’s disease.