Prof Mark Farrant

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Personal Profile

Name: Mark Farrant Email: m.farrant@ucl.ac.uk
Title: Prof Tel: 020 7679 4121
Department: Neuro, Physiology & Pharmacology Fax:
Position: Professor of Neuroscience Address: Medical Sciences Building, UCL, Gower Street, London, WC1E 6BT
Research Domain: Basic Life Sciences, Neuroscience Web Page: Personal Web Page

Profile

Research Description

Our group is interested in signalling in the central nervous system mediated by the amino acids glutamate and gamma-aminobutyric acid (GABA). The main focus of our research is on the ionotropic receptors for these neurotransmitters - multisubunit proteins that form ligand-gated ion channels allowing the passage across the neuronal membrane of anions (GABAA receptors) or cations (AMPA- and NMDA-type glutamate receptors). Their proper function is critical for the maintenance of appropriate neuronal excitability and they are targets for many clinically important drugs. Changes in glutamate receptors are key to learning and memory, while impaired function of GABAA receptors has been implicated in the genesis or expression of numerous brain disorders, including epilepsy.
We use patch-clamp electrophysiology in combination with molecular approaches to investigate the properties of heterologously expressed recombinant receptors and to examine synaptic and non-synaptic signalling in acute brain slices and neuronal cultures from wild-type and mutant or genetically modified mice. Our group has been at the forefront of studies characterizing NMDA receptor diversity, the origin of tonic GABAA receptor-mediated inhibition, and the regulation of calcium-permeable AMPA receptors. Most recently, we have been involved in collaborative studies to develop pharmacogenetic approaches to dissect the behavioural role of defined neuronal populations and in examination of the actions of TARPs (transmembrane AMPA receptor regulatory proteins). The overall aim of our work is to improve understanding of the pharmacological and biophysical properties of GABA and glutamate receptors, the regulation of their expression, and the functional significance of their heterogeneity in relation to synapses, circuits and behaviour.

Research Activities

Ionotropic GABA and glutamate receptor signalling

Education Description

UCL Collaborators

Prof Stuart Cull-Candy; Prof Matthew Walker

External Collaborators

Publications

    2014

    • Soto D, Coombs ID, Gratacòs-Batlle E, Farrant M, Cull-Candy SG (2014). Molecular Mechanisms Contributing to TARP Regulation of Channel Conductance and Polyamine Block of Calcium-Permeable AMPA Receptors.. J Neurosci, 34(35), 11673 - 11683. doi:10.1523/JNEUROSCI.0383-14.2014
    • Cais O, Herguedas B, Krol K, Cull-Candy SG, Farrant M, Greger IH (2014). Mapping the Interaction Sites between AMPA Receptors and TARPs Reveals a Role for the Receptor N-Terminal Domain in Channel Gating. Cell Reports, , - . doi:10.1016/j.celrep.2014.09.029

    2013

    • Studniarczyk D, Coombs I, Cull-Candy SG, Farrant M (2013). TARP gamma-7 selectively enhances synaptic expression of calcium-permeable AMPARs. Nature Neuroscience, , - . doi:10.1038/nn.3473
    • Bats C, Farrant M, Cull-Candy SG (2013). A role of TARPs in the expression and plasticity of calcium-permeable AMPARs: evidence from cerebellar neurons and glia.. Neuropharmacology, 74, 76 - 85. doi:10.1016/j.neuropharm.2013.03.037

    2012

    • Bats C, Soto D, Studniarczyk D, Farrant M, Cull-Candy SG (2012). Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons.. Nat Neurosci, 15(6), 853 - 861. doi:10.1038/nn.3107
    • Coombs ID, Soto D, Zonouzi M, Renzi M, Shelley C, Farrant M, Cull-Candy SG (2012). Cornichons modify channel properties of recombinant and glial AMPA receptors.. J Neurosci, 32(29), 9796 - 9804. doi:10.1523/JNEUROSCI.0345-12.2012
    • Shelley C, Farrant M, Cull-Candy SG (2012). TARP-associated AMPA receptors display an increased maximum channel conductance and multiple kinetically distinct open states. JOURNAL OF PHYSIOLOGY-LONDON, 590(22), 5723 - 5738. doi:10.1113/jphysiol.2012.238006
    • Eyre MD, Renzi M, Farrant M, Nusser Z (2012). Setting the time course of inhibitory synaptic currents by mixing multiple GABA(A) receptor α subunit isoforms.. J Neurosci, 32(17), 5853 - 5867. doi:10.1523/JNEUROSCI.6495-11.2012
    • BATS C, SOTO D, STUDNIARCZYK D, FARRANT M, CULL-CANDY SG (2012). Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons. Nature Neuroscience, , - . doi:10.1038/nn.3107

    2011

    • Zonouzi M, Renzi M, Farrant M, Cull-Candy SG (2011). Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells.. Nat Neurosci, 14(11), 1430 - 1438. doi:10.1038/nn.2942
    • Jackson AC, Milstein AD, Soto D, Farrant M, Cull-Candy SG, Nicoll RA (2011). Probing TARP modulation of AMPA receptor conductance with polyamine toxins.. J Neurosci, 31(20), 7511 - 7520. doi:10.1523/JNEUROSCI.6688-10.2011
    • Bright DP, Renzi M, Bartram J, McGee TP, MacKenzie G, Hosie AM, Farrant M, Brickley SG (2011). Profound desensitization by ambient GABA limits activation of δ-containing GABAA receptors during spillover.. J Neurosci, 31(2), 753 - 763. doi:10.1523/JNEUROSCI.2996-10.2011

    2010

    • Farrant M, Cull-Candy SG (2010). Neuroscience. AMPA receptors--another twist?. Science, 327(5972), 1463 - 1465. doi:10.1126/science.1187920
    • Farrant M, Cull-Candy SG (2010). AMPA receptors – another twist?. Science, 327, 1463 - 1464.

    2009

    • Wulff P, Schonewille M, Renzi M, Viltono L, Sassoe-Pognetto M, Badura A, Gao Z, Hoebeek FE, van Dorp S, Wisden W, Farrant M, De Zeeuw CI (2009). Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nature Neuroscience, 12(8), 1042 - 1049.
    • Zonouzi M, Coombs ID, Soto D, Renzi M, Farrant M, Cull-Candy SG (2009). TARPs control functional properties of calcium permeable AMPARs in cerebellar and olfactory bulb radial glia.
    • Shelley C, Soto D, Farrant M, Cull-Candy S (2009). Influence of the TARP gamma-4 on homomeric GluR1 AMPAR channels.
    • Kelly L, Farrant M, Cull-Candy SG (2009). Synaptic mGluR activation drives plasticity of calcium-permeable AMPA receptors. Nature Neuroscience, 12(5), 593 - 601.
    • Soto D, Coombs ID, Renzi M, Zonouzi M, Farrant M, Cull-Candy SG (2009). Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5.. Nat Neurosci, 12(3), 277 - 285. doi:10.1038/nn.2266
    • Soto D, Coombs ID, Renzi M, Zonouzi M, Farrant M, Cull-Candy SG (2009). Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5. NAT NEUROSCI, 12(6), 808 - 808. doi:10.1038/nn0609-808c

    2008

    • Ali R, Renzi M, Fukaya M, Watanabe M, Farrant M, Cull-Candy SG (2008). Failure of NMDAR activation during quantal release at cerebellar mossy fibre-granule cell synapses in adult mice..
    • Badura A, Schonewille M, Wulff P, Renzi M, Sassoè-Pognetto M, Gao Z, Hoebeek FE, Wisden W, Farrant M, De Zeeuw CI (2008). Inhibition in the cerebellar cortex – the role of interneurons in motor learning..
    • Aller MI, Ali R, Brickley S, Wulff P, Korpi ER, Farrant M, Wisden W (2008). Phasic inhibition onto cerebellar granule cells.
    • Soto D, Coombs ID, Zonouzi M, Farrant M, Cull-Candy SG (2008). Effects of TARPs on basic properties of calcium-permeable AMPA receptors.

    2007

    • Soto D, Coombs ID, Kelly L, Farrant M, Cull-Candy SG (2007). Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors. Nature Neuroscience, 10(10), 1260 - 1267.
    • Silver RA, Farrant M (2007). Neurotransmitter-gated channels in dendrites. In Stuart G, Spruston N, Häusser M (Ed.), Dendrites (pp. 190 - 223). : Oxford University Press.
    • Wulff P, Goetz T, Leppa E, Linden AM, Renzi M, Swinny JD, Vekovischeva OY, Sieghart W, Somogyi P, Korpi ER, Farrant M, Wisden W (2007). From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nature Neuroscience, 10, 923 - 929.
    • Renzi M, Farrant M, Cull-Candy SG (2007). Climbing-fibre activation of NMDA receptors in Purkinje cells of adult mice.. The Journal of Physiology, Sep 27;, Epub - ahead of p. doi:10.1113/jphysiol.2007.141531
    • Farrant M, Kaila K (2007). The cellular, molecular and ionic basis of GABAA receptor signalling. In Tepper JM, Abercrombie ED, Bolam JP (Ed.), Gaba and the Basal Ganglia - From Molecules to Systems (pp. 59 - 87). : Elsevier/Academic Press. doi:10.1016/S0079-6123(06)60005-8
    • Soto D, Coombs ID, Kelly L, Farrant M, Cull-Candy SG (2007). Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors (vol 10, pg 1260, 2007). NAT NEUROSCI, 10(12), 1634 - 1634. doi:10.1038/nn1207-1634a
    • Farrant M (2007). Differential activation of GABAA receptor subtypes. In Enna S, Mohler H (Ed.), The GABA Receptors (pp. 87 - 110). : Humana Press Inc..

    2006

    • Cull-Candy S, Kelly L, Farrant M (2006). Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond.. Current Opinion in Neurobiology, 16, 288 - 297.

    2005

    • Farrant M, Nusser Z (2005). Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors.. Nature Reviews Neuroscience, 6, 215 - 229. doi:10.1038/nrn1625
    • Ali R, Aller M, Luscher B, Brickley SG, Korpi ER, Cull-Candy SG, Wisden W, Farrant M (2005). Loss of inhibitory postsynaptic currents following selective ablation of the GABAA receptor γ2 subunit in cerebellar granule cells of mice..

    2004

    • Cathala L, Brickley S, Cull-Candy S, Farrant M (2004). Maturation of EPSCs and intrinsic membrane properties enhances precision at a cerebellar synapse (vol 23, pg 6074, 2003). J NEUROSCI, 24(9), 2343 - 2343.
    • Kelly L, Clark BA, Farrant M, Cull-Candy SG (2004). Changes in rectification and channel conductance suggest an increase in Ca2+-impermeable AMPARs at the maturing parallel fiber-stellate cell synapse..

    2003

    • Aller MI, Jones A, Merlo D, Paterlini M, Meyer AH, Amtmann U, Brickley S, Jolin H, McKenzie AN, Monyer H, Farrant M, Wisden W (2003). Cerebellar granule cell Cre recombinase expression. Genesis, 36(2), 97 - 103.
    • Cathala L, Brickley S, Cull-Candy S, Farrant M (2003). Maturation of EPSCs and intrinsic membrane properties enhances precision of a cerebellar synapse. Journal of Neuroscience, 23(14), 6074 - 6085.
    • Farrant M, Brickley SG (2003). Properties of GABAA receptor-mediated transmission at newly formed Golgi-granule cell synapses in the cerebellum. Neuropharmacology, 44(2), 181 - 189.
    • Stell BM, Brickley SG, Tang CY, Farrant M, Mody I (2003). Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 14439 - 14444.

    2001

    • Cull-Candy S, Brickley S, Farrant M (2001). NMDA receptor subunits: diversity, development and disease.. Curr Opin Neurobiol, 11(3), 327 - 335.
    • Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M (2001). Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature, 409, 88 - 91.
    • Farrant M (2001). Amino acids: inhibitory. In Webster RA (Ed.), Neurotransmitters, Drugs and Brain Function (pp. 225 - 250). : Wiley.
    • Wisden W, Farrant M (2001). Insights into GABAA receptor complexity from the study of cerebellar granule cells. In Egebjerg J, Schoesboe A, Krogsgaard-Larsen P (Ed.), Glutamate and GABA Receptors and Transporters (pp. 189 - 201). : Taylor and Francis.
    • Brickley SG, Farrant M, Swanson GT, Cull-Candy SG (2001). CNQX increases GABA-mediated synaptic transmission in the cerebellum by an AMPA/kainate receptor-independent mechanism. Neuropharmacology, 41, 730 - 736.
    • Cathala L, Brickley S, Farrant M, Cull-Candy S (2001). Developmental changes in AMPA receptor-mediated synaptic transmission at mossy fibre-granule cell synapses in the cerebellum..

    2000

    • Misra C, Brickley SG, Farrant M, Cull-Candy SG (2000). Identification of subunits contributing to synaptic and extrasynaptic NMDA receptors in Golgi cells of the rat cerebellum. The Journal of Physiology, 524, 147 - 162.
    • Merlo D, Brickley SG, Farrant M, Cull-Candy SG, Wisden W (2000). GABAA receptor diversity: A view from the cerebellum. In Martin DL, Olsen RW (Ed.), GABA in the Nervous System (pp. 369 - 382). : Lippincott, Williams and Wilkins.

    1999

    • Misra C, Brickley SG, Farrant M, Cull-Candy SG (1999). Synaptic NMDA receptors in Golgi cells of the rat cerebellum.
    • Brickley SG, Cull-Candy SG, Farrant M (1999). Single-channel properties of synaptic and extrasynaptic GABAA receptors suggest differential targeting of receptor subtypes. Journal of Neuroscience, 19, 2960 - 2973.
    • Silver RA, Farrant M (1999). Neurotransmitter-gated channels in dendrites. In Stuart G, Spruston N, Häusser M (Ed.), Dendrites (pp. 114 - 138). : Oxford University Press.

    1998

    • Cull-Candy SG, Brickley SG, Misra C, Feldmeyer D, Momiyama A, Farrant M (1998). NMDA receptor diversity in the cerebellum: identification of subunits contributing to functional receptors.. Neuropharmacology, 37(10-11), 1369 - 1380.

    1997

    • Nusser Z, CullCandy S, Farrant M (1997). Postsynaptic GABA(A) receptor occupancy depends on receptor number at synapses on stellate cells in the rat cerebellum. J PHYSIOL-LONDON, 501P, P10 - P11.
    • Nusser Z, Cull-Candy S, Farrant M (1997). Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude.. Neuron, 19(3), 697 - 709.
    • Nusser Z, Cull-Candy SG, Farrant M (1997). Postsynaptic GABAA receptor occupancy depends on receptor number at synapses on stellate cells in the rat cerebellum..
    • Clark BA, Farrant M, Cull-Candy SG (1997). A direct comparison of the single-channel properties of synaptic and extrasynaptic NMDA receptors. Journal of Neuroscience, 17, 107 - 116.
    • Brickley S, Farrant M, CullCandy S (1997). CNQX increases the frequency of GABA(A) receptor-mediated synaptic currents in granule cells of the rat cerebellum. J PHYSIOL-LONDON, 501P, P11 - P11.

    1996

    • Brickley SG, Cull-Candy SG, Farrant M (1996). Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors.. The Journal of Physiology, 497(3), 753 - 759.
    • Silver RA, Farrant M, CullCandy SG (1996). Filtering of synaptic currents estimated from the time course of NMDA channel opening at the rat cerebellar mossy fibre granule cell synapse.
    • Farrant M, Brickley SG, CullCandy SG (1996). Methods for comparing the conductance and kinetic properties of synaptic and extrasynaptic receptors.

    1995

    • Cull-Candy SG, Farrant M, Feldmeyer D (1995). NMDA channel conductance: a user’s guide. In Wheal H, Thomson A (Ed.), Excitatory Amino Acids and Synaptic Transmission (pp. 121 - 132). : Academic Press Ltd.
    • BRICKLEY SG, FARRANT M, CULLCANDY SG (1995). SINGLE-CHANNEL CONDUCTANCE OF SYNAPTICALLY ACTIVATED GABA(A) RECEPTORS IN RAT CEREBELLAR GRANULE CELLS IN SLICES. J PHYSIOL-LONDON, 483P, P60 - P61.
    • BRICKLEY SG, FARRANT M, CULLCANDY SG (1995). APPARENT HETEROGENEITY OF EXTRASYNAPTIC GABA(A) RECEPTORS IN GRANULE CELLS OF THE RAT CEREBELLUM. J PHYSIOL-LONDON, 487P, P52 - P53.
    • FARRANT M, KANEDA M, CULLCANDY SG (1995). BENZODIAZEPINE MODULATION OF GABA-ACTIVATED CURRENTS IN GRANULE CELLS OF THE RAT CEREBELLUM. J PHYSIOL-LONDON, 489P, P17 - P17.
    • Kaneda M, Farrant M, Cull-Candy SG (1995). Whole-cell and single-channel currents activated by GABA and glycine in granule cells of the rat cerebellum.. The Journal of Physiology, 485(2), 419 - 435.
    • FELDMEYER D, FARRANT M, CULLCANDY SG (1995). MACROSCOPIC KINETIC-PROPERTIES OF NMDA RECEPTORS IN PATCHES FROM GRANULE CELLS OF THE RAT CEREBELLUM. J PHYSIOL-LONDON, 489P, P14 - P15.

    1994

    • KANEDA M, FARRANT M, CULLCANDY SG (1994). GABA-ACTIVATED AND GLYCINE-ACTIVATED CURRENTS IN GRANULE CELLS OF THE RAT CEREBELLUM. J PHYSIOL-LONDON, 476P, P68 - P68.
    • Farrant M, Feldmeyer D, Takahashi T, Cull-Candy SG (1994). NMDA-receptor channel diversity in the developing cerebellum. Nature, 368, 335 - 339.
    • FARRANT M, CLARK BA, CULLCANDY SG (1994). A DIRECT COMPARISON OF SYNAPTIC AND SOMATIC NMDA CHANNELS IN RAT CEREBELLAR GRANULE CELLS. J PHYSIOL-LONDON, 480P, P25 - P25.

    1993

    • FARRANT M, CULLCANDY S (1993). NEUROBIOLOGY - GABA RECEPTORS, GRANULE CELLS AND GENES. NATURE, 361(6410), 302 - 303.
    • Farrant M, Cull-Candy S (1993). GABA receptors, granule cells and genes.. Nature, 361(6410), 302 - 303. doi:10.1038/361302a0
    • FARRANT M, FELDMEYER D, KOBAYASHI S, TAKAHASHI T, CULLCANDY SG (1993). NMDA RECEPTOR CHANNELS OF DEVELOPING GRANULE CELLS IN RAT THIN CEREBELLAR SLICES. J PHYSIOL-LONDON, 467, P272 - P272.
    • Colquhoun D, Farrant M (1993). News & Views. Molecular Pharmacology: The binding issue.. Nature, 366, 510 - 511. doi:10.1038/366510b0
    • Farrant M, Cull-Candy SG (1993). News & Views. Neurobiology: GABA receptors granule cells and genes.. Nature, 361, 302 - 303.

    1991

    • Farrant M, Cull-Candy SG (1991). Excitatory amino acid receptor-channels in Purkinje cells in thin cerebellar slices.. Proceedings of the Royal Society B: Biological Sciences, 244(1311), 179 - 184.

    1989

    • Farrant M, Webster RA (1989). GABA antagonists: their use and mechanisms of action. In Boulton AA, Baker GB, Jurio AV (Ed.), Drugs as Tools in Neurotransmitter Research (pp. 161 - 219). : Humana Press Inc..
    • Farrant M, Webster RA (1989). Compartmental distribution of endogenous amino acids in the substantia nigra of the rat.. Brain Research, 480(1-2), 344 - 348.
    • Farrant M, Webster RA (1989). Neuronal activity, amino acid concentration and amino acid release in the substantia nigra of the rat after sodium valproate.. Brain Research, 480(1-2), 344 - 348.
    • Farrant M, Webster RA (1989). Neuronal activity, amino acid concentration and amino acid release in the substantia nigra of the rat after sodium valproate.. Brain Res, 504(1), 49 - 56.

    1988

    • Gyenes M, Farrant M, Farb DH (1988). “Run-down” of γ-aminobutyric acidA receptor function during whole-cell recording: a possible role for phosphorylation.. Molecular Pharmacology, 34(6), 719 - 723.

    1987

    • Farrant M (1987). Inhibitory neurotransmission and amino acid release in the substantia nigra of the rat. Ph.D., University of London..
    • Farrant M, Zia-Gharib F, Webster RA (1987). Automated pre-column derivatization with o-phthalaldehyde for the determination of neurotransmitter amino acids using reversed-phase liquid chromatography.. J Chromatogr, 417(2), 385 - 390.