Department of Neuroscience, Physiology & Pharmacology
Ionotropic glutamate and GABA receptor signalling
We are interested in neurotransmission in the brain and how the multiplicity of receptor subunits and accessory proteins forming ionotropic AMPA-type glutamate receptors and GABAA receptors generates heterogeneity in both excitatory and inhibitory signalling. We study the molecular basis of this heterogeneity and its contribution to the function of receptors, synapses and circuits, and to the aetiology of disease. 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.
We are currently investigating:
· the functional effects of AMPA receptor and auxiliary protein variants linked to psychiatric illness
· the mechanisms of action of auxiliary proteins that regulate the number and function of calcium-permeable AMPA receptor subtypes
· the actions of GABAA receptor interacting proteins
Davenport EC, Pendolino V, Kontou G, McGee TP,
Sheehan DF, Lopez-Domenech G, Farrant M, Kittler JT (2017) An essential
role for the tetraspanin LHFPL4 in the cell type-specific targeting and
clustering of synaptic GABAA receptors. Cell Reports (in press).
Coombs ID, MacLean DM, Jayaraman V, Farrant M, Cull-Candy SG (2017).
Dual effects of TARP ?-2 on glutamate efficacy can account for AMPA receptor
autoinactivation Cell Reports 20:1123-35.
Sullivan, SJ, Farrant M, Cull-Candy SG (2017). TARP ?-2 is required for
inflammation-associated AMPA receptor plasticity within lamina II of the spinal
cord dorsal horn. Journal of Neuroscience 37: 6007-20.
McGee TP, Bats C, Farrant M, Cull-Candy SG (2015). Auxiliary subunit GSG1L acts to suppress calcium-permeable AMPA receptor function. Journal of Neuroscience 35: 16171-79.
Zonouzi M, Scafidi J, Li P, McEllin B, Edwards J, Dupree JL, Harvey L, Sun D, Hübner CA, Cull-Candy SG, Farrant M, Gallo V (2015) GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury. Nature Neuroscience 18: 674-82
Rigby M, Cull-Candy SG, Farrant M (2015) Transmembrane AMPAR regulatory protein γ-2 is required for the modulation of GABA release by presynaptic AMPARs. Journal of Neuroscience 35: 4203-14.
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 9: 728-40.
Studniarczyk, D, Coombs I, Cull-Candy, SG, Farrant, M (2013) TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs. Nature Neuroscience 16: 1266-74.
Bats M, Farrant M and Cull-Candy SG. (2012) Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons. Nature Neuroscience 15, 853-61.
Eyre MD, Renzi M, Farrant M and Nusser Z (2012) Setting the time course of inhibitory synaptic currents by mixing multiple GABAA receptor subunit isoforms. The Journal of Neuroscience 32, 5853-67.
Zonouzi M, Renzi M, Farrant M and Cull-Candy SG (2011) Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells. Nature Neuroscience 14, 1430-38.
Jackson AC, Milstein AD, Soto D, Farrant M, Cull-Candy SG and Nicoll RA. (2011) Probing TARP modulation of AMPA receptor conductance with polyamine toxins. The Journal of Neuroscience 31, 7511-20.
Bright DP, Renzi M, Bartram J, McGee TP, MacKenzie G, Hosie AM, Farrant M and Brickley SG. (2011) Profound desensitization by ambient GABA limits activation of δ-containing GABAA receptors during spillover. The Journal of Neuroscience 31, 753-63.
Wulff P, Schonewille M, Renzi M, Viltono L, Sassoè-Pognetto M, Badura A, Gao Z, Hoebeek FE, van Dorp S, Wisden W, Farrant M and de Zeeuw CI. (2009) Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nature Neuroscience 12, 1042-9.
Soto D, Coombs ID, Renzi M, Zonouzi M, Farrant M and Cull-Candy SG. (2009) Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, γ-5. Nature Neuroscience 12, 277-85.
Kelly L, Farrant M and Cull-Candy SG. (2009) Synaptic mGluR activation drives plasticity of calcium-permeable AMPA receptors. Nature Neuroscience 12, 593-601.
Wulff P, Goetz T, Leppä E, Linden A-M, Renzi M, Swinny JD, Vekovischeva OY, Sieghart W, Somogyi P, Korpi ER, Farrant M and Wisden W. (2007) From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nature Neuroscience 10, 923-9.
Soto D, Coombs ID, Kelly L, Farrant M and Cull-Candy SG. (2007) Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors. Nature Neuroscience 10, 1260-7.