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dc.contributor.authorHelassa, Nen_US
dc.contributor.authorDürst, CDen_US
dc.contributor.authorCoates, Cen_US
dc.contributor.authorKerruth, Sen_US
dc.contributor.authorArif, Uen_US
dc.contributor.authorSchulze, Cen_US
dc.contributor.authorWiegert, JSen_US
dc.contributor.authorGeeves, Men_US
dc.contributor.authorOertner, TGen_US
dc.contributor.authorTörök, Ken_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-03-06T09:36:17Z
dc.date.issued2018-05-22en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29735711en_US
dc.identifier1720648115en_US
dc.identifier.citationProc Natl Acad Sci U S A, 2018, 115 (21), pp. 5594 - 5599en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3141
dc.identifier.eissn1091-6490en_US
dc.identifier.doi10.1073/pnas.1720648115en_US
dc.description.abstractGlutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.en_US
dc.format.extent5594 - 5599en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectglutamateen_US
dc.subjecthippocampusen_US
dc.subjectsynaptic transmissionen_US
dc.subjecttwo-photon imagingen_US
dc.subjectAnimalsen_US
dc.subjectGlutamic Aciden_US
dc.subjectHippocampusen_US
dc.subjectMaleen_US
dc.subjectNeuronal Plasticityen_US
dc.subjectPatch-Clamp Techniquesen_US
dc.subjectPresynaptic Terminalsen_US
dc.subjectPyramidal Cellsen_US
dc.subjectRatsen_US
dc.subjectRats, Wistaren_US
dc.subjectSynapsesen_US
dc.subjectSynaptic Transmissionen_US
dc.titleUltrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1073/pnas.1720648115en_US
rioxxterms.licenseref.startdate2018-05-22en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfProc Natl Acad Sci U S Aen_US
pubs.issue21en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Cell Division
pubs.publication-statusPublisheden_US
pubs.volume115en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCell Divisionen_US
dc.contributor.icrauthorCoates, Catherineen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/