Glutamate receptor channels and fast synaptic transmission in the brain
Stuart G. Cull-Candy, FMedSci, FRS
|Professor of Neuroscience/Gaddum Professor of Pharmacology|
|Tel: 020 7679 3766|
Professor S G Cull-Candy, FMedSci, FRS, holds the established Gaddum Chair of Pharmacology, and a personal Chair in Neuroscience at UCL. He also holds a Royal Society - Wolfson Research position. He received his MSc from UCL, and his PhD from the University of Glasgow. After working as a Royal Society Exchange Fellow at the University of Lund with Prof Stephen Thesleff, he held a Beit Memorial Research Fellowship in UCL's Biophysics Department with Sir Bernard Katz and Prof Ricardo Miledi. He was previously a Wellcome Trust Reader and then Professor of Pharmacology. He has been an Editorial Advisor to Nature, and served on the Editorial Boards of various journals including Neuron, Journal of Physiology and as a Reviewing Editor on Journal of Neuroscience. He currently is Section Editor on Current Opinions in Neurobiology, and a Member of the Faculty of 1000. He has served on the Medical Research Council Neuroscience Board and the Wellcome Trust's International Interest Group Grants Committee. Currently he is a member of the Royal Society's University Research Fellowships Committee, and the Leverhulme Trust Senior Research Fellowships panel. He was awarded the GL Brown Prize by the UK Physiological Society, and was appointed a Howard Hughes International Scholar in 1993 (one of only 20 in the UK). He is a Fellow of the Royal Society, the Academy of Medical Sciences and the Pharmacological Society. In 2002 he was also awarded a Royal Society Wolfson Research merit award to allow him to concentrate on his Research. His research focuses on understanding molecular and functional properties of glutamate receptor channels underlying fast synaptic transmission in the brain. He has been a keen advocate of patch-clamp recording techniques combined with molecular methods for investigating central synaptic transmission. Stuart Cull-Candy FRS UCL 2009
Our research focuses mainly on understanding how nerve impulses are transmitted between neurons in the brain. In the central nervous system, neighbouring neurons are in close proximity, but they are not usually in close enough contact for the electrical impulse to jump across the intervening gap between cells. To carry the impulse, a majority of excitatory neurons in the brain use the transmitter glutamate, which is thought to be packaged in presynaptic vesicles, a proportion of which release their contents into the synaptic cleft in response to the invading nerve impulse. Glutamate diffusing across the cleft, binds to specific receptor molecules embedded in the postsynaptic cell - that contain an integral ion channel.
At many excitatory glutamate-synapses, and inhibitory GABA synapses, the transmitter released into the synaptic cleft activates more then one type of receptor in the postsynaptic membrane. Indeed, synaptic signaling in the CNS is made a lot more versatile by the fact that these receptors can be composed of a variety of different subunits that critically determine the functional properties of the individual receptors and so of synaptic transmission. It is therefore a major challenge to understand how individual receptor subunits influence basic properties of transmission at specific synapses, and how subunit diversity enables various dynamic changes in synaptic function. This is an essential step towards the understanding of signalling in the brain.
The research group headed by Prof Stuart Cull-Candy and Prof Mark Farrant is funded by two concurrent long-term Programme Grants from the Wellcome Trust. The group uses a combination of electrophysiological and molecular biology techniques. The work uses patch clamp recording techniques, such as high resolution recording and analysis of single ion channels, and analysis of synaptic currents, to investigate the reactions by which the transmitter receptor complex leads to the opening of ion channels, and also to measure the effects of other factors, such as addition of blocking drugs, alteration of the chemical constituents of the membrane, etc. which control these reactions. Our general aim is to obtain fundamental knowledge about synaptic transmission at the molecular level, as well to elucidate the mechanisms by which medicines affect cellular and molecular brain function. Recently, we have become interested in understanding the critical role of the transmembrane AMPA receptor regulatory proteins (TARPS) and other auxiliary AMPA receptor subunits in governing basic properties of AMPARs, particularly the calcium permeable (GluR2 lacking) subtypes that are involved in synaptic plasticity, and a variety of important neurological disorders (Soto et al 2007, Nature Neuroscience 10, 1260-1267; Cull-Candy et al 2006, Current Opinion Neurobiology 16, 288-297; Soto et al 2009, Nature Neuroscience 12, 277-285).
Together with several other labs at UCL, Prof Cull-Candy received a Joint Infrastructural Award of £9m, enhancing expansion of Molecular and Cellular Neuroscience at UCL. Research in the Department at UCL was top rated in the latest Research Assessment exercise (RAE).
- Kelly, L., Farrant, M. and Cull-Candy, S.G. (2009) Synaptic mGluR activation drives plasticity of calcium-permeable AMPA receptors Nature Neuroscience 12, 593-601.
- Soto, D., Coombs, I.D, Renzi, M., Zonouzi, M., Farrant, M and CullCandy, S G (2009) Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5. Nature Neuroscience 12, 277-285.
- Soto, D., Coombs, I.D, Kelly, L. Farrant, M. and Cull-Candy, S.G. (2007) Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors Nature Neuroscience 10, 1260-1267.
- Renzi, M., Farrant, M. and Cull-Candy, S.G. (2007) Climbing-fibre activation of NMDA receptors in Purkinje cells of adult mice Journal of Physiology 585: 91-101.
- Cull-Candy, S. & Klein R – Editors (2007) Signaling Mechanisms - Current Opinions in Neurobiology 17
- Cull-Candy, S., Kelly, L. & and Farrant, M. (2006) Regulation of Ca 2+-permeable AMPA receptors: synaptic plasticity and beyond. Current Opinion in Neurobiology 16, 288-297
- Liu, S.J & Cull-Candy, S.G. (2005) Subunit interaction with PICK and GRIP controls Ca 2+-permeability of AMPARs at cerebellar synapses. Nature Neuroscience 8, 768-775
- Cathala, L., Holderith, N.B. Nusser, Z., DiGregorio, D and Cull-Candy, S.G. (2005) Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs. Nature Neuroscience 8, 1310-1318
- Cull-Candy, S.G & Leszkiewicz , D (2004) Role of distinct NMDA receptor subtypes at central synapses Science (STKE Review) 16, 1-9
- Brickley SG, Misra C, Mok MH, Mishina M, Cull-Candy SG. (2003) NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites. J Neurosci. 23 (12): 4958-66. Abstract (Link to PubMed)
- Liu, S-Q. J. & Cull-Candy, S. G. (2002) Activity-dependent change in AMPA receptor properties in cerebellar stellate cells. J. Neurosci. 22: 3881–3889. Abstract (Link to PubMed)
- Brickley, S.G, Revilla, V., Cull-Candy, S.G., Wisden, W & Farrant, M. (2001) Adaptive regulation of neuronal excitability by a voltage-independent K+ conductance. Nature 409, 88-91. Abstract (Link to PubMed)
- Liu, S-Q. J. & Cull-Candy, S. G. (2000) Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405, 454-458 Abstract (Link to PubMed)