Centre for Discovery Brain Sciences
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Prof David Wyllie

We study neurotransmitter action in central neurons to understand normal synaptic function and its dysfunction in models of neurodevelopmental and neurodegenerative diseases.

Professor David Wyllie

Professor of Ion Channel Physiology and Pharmacology; Director, Centre for Discovery Brain Sciences

  • Hugh Robson Building
  • 15 George Square
  • Edinburgh, EH8 9XD

Contact details

Personal profile

  • 2018 - Present: Senior Editor, The Journal of Physiology
  • 2017 - Present: Director, Centre for Discovery Brain Sciences
  • 2015 - 2018:  Reviewing Editor, The Journal of Physiology
  • 2015 - 2017: Director, Centre for Integrative Physiology
  • 2008 - 2011:  Member, Wellcome Trust Molecular & Cellular Neuroscience Funding Committee
  • 2006 - 2014:  Trustee of The Physiological Society
  • 2002 - 2009:  Editorial Board Member, British Journal of Pharmacology
  • 1994 - 1999:  Royal Society University Research Fellow, Dept of Pharmacology, UCL
  • 1992 - 1994:  SERC/NATO post-doctoral researcher, Dept of Pharmacology, University of California, San Francisco

Research Theme


Prof David Wyllie's research briefing

My long-standing research interest is in ligand-gated ion channels (LGICs) – specialized pore-forming membrane proteins that are activated by neurotransmitters during ‘fast’ chemical synaptic transmission.  In particular my lab studies LGICs activated by L-glutamate – the major excitatory neurotransmitter in the mammalian brain.

Although glutamate activates several different classes of LGIC one in particular, the N-methyl-D-aspartate receptor (NMDAR) has been a major focus for our research.  Through electrophysiological studies, my lab has contributed significantly to our understanding of the structure-function properties and physiological roles of the various subtypes of NMDARs.

NMDARs play pivotal roles in both normal and abnormal brain function.  In early life for instance, they ensure that the correct wiring pattern is laid down in the developing brain.  Furthermore, activation of NMDARs is required to learn certain tasks and store memories.  However, both over- and under-activation of NMDARs can be deleterious for normal brain function.  For example, during a stroke excessive activation of NMDARs contributes significantly to neuronal loss, while NMDAR dysfunction is thought to contribute to diseases such as Alzheimer’s, Parkinson’s and Schizophrenia.  More recently it is now recognised that de novo mutations in the protein sequence of NMDARs can lead to intellectual disability.  Directly related to our structure-function studies of NMDARs we use pre-clinical models of single gene causes of neurodevelopmental disorders (such as fragile X syndrome) to study the properties of altered synaptic function and to assess the extent to which pharmacological intervention can ameliorate the changes that are observed in such models.

A more recent focus of our research is the electrophysiological and functional characterization of defined neuronal and glial populations derived from human embryonic stem cells and induced pluripotent stem cells and specifically those from individuals suffering from neurodevelopmental and neurodegenerative diseases. Our work seeks to assess the electrophysiological profile of such neurons in order to further our understanding of these debilitating diseases.

Our overall aim is to develop an integrated approach to research that begins with the study of single protein molecules and synaptic function and extends, through collaboration with colleagues, to whole animal studies with an ultimate goal of the clinical study and treatment of disease.


We gratefully acknowledge present and past support for our research from the following:

Team members


Selected Publications

Selvaraj BT, Livesey MR, Zhao C, Gregory J, James OT, Cleary  EM, Chouhan AK, Gane A, Perkins EM, Dando O, Lillico SG, Lee Y-B, Nishimura AL, Poreci U, Thankamony S, Pray M, Vasistha NA, Magnani D, Borooah S, Burr K, Story D, McCampbell A, Shaw CE, Kind PC, Aitman TJ, Whitelaw CBA, Wilmut I, Smith C, Miles GB, Hardingham GE, Wyllie DJA & Chandran S (2018).  C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nat Commun 9, 347 doi: 10.1038/s41467-017-02729-0 PMID: 29367641

Booker SA, Loreth D, Gee AL, Watanabe M, Kind PC, Wyllie DJA, Kulik Á, &Vida I (2018).  Postsynaptic GABABRs inhibit L-type calcium channels and abolish long-term potentiation in hippocampal somatostatin interneurons.  Cell Rep 22, 36-43. PMID: 29298431

Thomson SR, Seo SS, Barnes SA, Louros SR, Muscas M, Dando O, Kirby C, Wyllie DJA, Hardingham GE, Kind PC & Osterweil EK (2017). Cell type-specific translation profiling reveals a novel strategy for treating fragile X syndrome. Neuron 95, 550-563.  PMID: 28772121

McQueen J, Ryan TJ, McKay S, Marwick K, Carpanini S, Wishart TM, Gillingwater TH, Manson JC, Wyllie DJA, Grant SGN, McColl B, Komiyama NH & Hardingham GE (2017).  Pro-death NMDA receptor signaling is promoted by the GluN2B C-terminus independently of DAPK1. eLife  6:e17161 PMID: 28731405

Hasel P, Dando O, Jiwaji Z, Baxter P, Todd AC, Heron S, Márkus NM, McQueen J, Hampton DW, Torvell M, Tiwari SS, McKay S, Eraso-Pichot A, Zorzano A, Masgrau R, Galea E, Chandran S, Wyllie DJA, Simpson TI & Hardingham GE (2017). Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.  Nat Commun 8, 15132  doi: 10.1038/ncomms15132 PMID: 28462931

Marwick KFM, Parker P, Skehel P, Hardingham G & Wyllie DJA (2017).  Functional assessment of the NMDA receptor variant GluN2AR586K Wellcome Open Res doi: 10.12688/wellcomeopenres.10985.1  PMID: 28459106

Currie S, Luz L, Booker S, Wyllie DJA, Kind PC & Daw M (2017).  Reduced local input to fast-spiking interneurons in the somatosensory cortex in the GABAA γ2 R43Q mouse model of absence epilepsy.  Epilepsia 58, 597-607.  PMID: 28195311 

Booker SA, Campbell GR, Mysiak KS, Brophy PJ, Kind PC, Mahad DJ & Wyllie DJA (2017).  Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses. J Physiol 595, 2147-2160. PMID: 28083896

Perkins EM, Suminaite D, Clarkson YL, Lee SK, Lyndon AR, Rothstein JD, Wyllie DJA, Tanaka K & Jackson M (2016).  Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.  Hum Mol Genet 20, 4448-4461. PMID: 28173092

Livesey MR, Magnani D, Cleary EM, James OT, Selvaraj BT, Burr K, Vasistha NA, Story D, Shaw CE, Kind PC, Hardingham GE, Wyllie DJA & Chandran S (2016).  Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes.  Stem Cells 34, 1040-1053.  PMID: 26763608

Livesey MR, Magnani D, Hardingham GE, Chandran S & Wyllie DJA (2016).  Functional properties of in vitro excitatory cortical neurones derived from human pluripotent stem cells. J Physiol 594, 6573-6582.  PMID: 26608229

Barnes SA, Wijetunge LS, Jackson AD, Katsanevaki D, Osterweil EK, Komiyama NH, Grant SGN, Bear MF, Nägerl UV, Kind PC & Wyllie DJA (2015).  Convergence of hippocampal pathophysiology in Syngap+/- and Fmr1-/y mice.  J Neurosci 35, 15073-15081. PMID: 26558778

Till SM, Asiminas A, Jackson AD, Katsanevaki D, Barnes SA, Osterweil EK, Bear MF, Chattarji S, Wood ER, Wyllie DJA & Kind PC (2015).  Conserved hippocampal cellular pathophysiology but distinct behavioural deficits in a new rat model of FXS.  Hum Mol Genet 24, 5977-5984. PMID: 26243794

James OT, Livesey MR, Qiu J, Dando O, Bilican B, Haghi G, Rajan R, Burr K, Hardingham GE, Chandran S, Kind PC, & Wyllie DJA. (2014). Ionotropic GABA and glycine receptor subunit composition in human pluripotent stem cell-derived excitatory cortical neurones.  J Physiol 592, 4353-4363. PMID: 25172951

Livesey MR, Bilican B, Qiu J, Rzechorzek NM, Haghi G, Burr K, Hardingham GE, Chandran & Wyllie DJA (2014).  Maturation of AMPAR composition and the GABAAR reversal potential in hPSC-derived cortical neurons.  J Neurosci 34, 4070-4075. PMID: 24623784

McMahon AC, Barnett MW, Stoney PN, Collins MO, O’Leary TS, Papadia S,  Choudhary JS, Komiyama NH, Grant SGN, Hardingham GE, Wyllie DJA & Kind PC (2012).  SynGAP isoforms exert opposing effects on synaptic strength. Nat Commun 3:900  DOI: 10.1038/ncomms1900 PMID: 22692543

Puddifoot CA, Martel M-A, Soriano FX, Camacho A, Vidal-Puig A, Wyllie DJA & Hardingham GE (2012). PGC-1α negatively regulates extrasynaptic NMDAR activity and excitotoxicity. J Neurosci 32, 6995-7000.   PMID: 22593067

Edman S, McKay S, MacDonald LJ, Samadi M, Livesey MR, Hardingham GE & Wyllie DJA (2012).  TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner.  Neuropharmacology 63, 441-449.  PMID: 22579927

Martel M-A, Ryan TJ, Bell KFS, Fowler JH, McMahon A, Al-Mubarak B, Komiyama NH, Horsburgh K, Kind PC, Grant SGN, Wyllie DJA & Hardingham GE (2012).  The subtype of GluN2 C-terminal domain determines the response to excitotoxic insults. Neuron 74, 543-556.  PMID: 22578505