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dc.contributor.authorBeltran Matas, Pablo
dc.contributor.authorHartveit, Espen
dc.contributor.authorVeruki, Margaret Lin
dc.date.accessioned2021-08-13T07:36:24Z
dc.date.available2021-08-13T07:36:24Z
dc.date.created2021-06-24T19:20:34Z
dc.date.issued2021
dc.identifier.issn0953-816X
dc.identifier.urihttps://hdl.handle.net/11250/2767701
dc.description.abstractThe NMDA receptors (NMDARs) expressed by AII and A17 amacrine cells, the two main inhibitory interneurons of the rod pathway microcircuit in the mammalian retina, are exclusively extrasynaptic, activated by ambient levels of glutamate, and molecularly distinct, with AII and A17 amacrines expressing GluN2B- and GluN2A-containing receptors, respectively. This important sensory microcircuit thus provides a unique model to study the activation and function of extrasynaptic NMDARs. Here, we investigated the sources of glutamate and the endogenous co-agonists (d-serine or glycine) that activate these distinct populations of NMDARs. With acute slices from rat retina, we used whole-cell voltage-clamp recording and measurement of current noise to monitor levels of NMDAR activity. Pre-incubation of retina with bafilomycin A1 (an inhibitor of neurotransmitter uptake into synaptic vesicles) abolished NMDAR-mediated noise in AII, but not A17 amacrines, suggesting a vesicular source of glutamate activates AII NMDARs, whereas a non-vesicular source activates A17 NMDARs. Pre-incubation of retina with l-methionine sulfoximine (an inhibitor of glutamine synthetase) also abolished NMDAR-mediated noise in AII, but not A17 amacrines, suggesting a neuronal source of glutamate activates AII NMDARs, whereas a glial source activates A17 NMDARs. Enzymatic breakdown of d-serine reduced NMDAR-mediated noise in AII, but not A17 amacrines, suggesting d-serine is the endogenous co-agonist at AII, but not A17 NMDARs. Our results reveal unique characteristics of these two populations of extrasynaptic NMDARs. The differential and independent activation of these receptors is likely to provide specific contributions to the signal processing and plasticity of the cellular components of the rod pathway microcircuit.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.subjectNevrovitenskapen_US
dc.subjectNeuroscienceen_US
dc.titleDifferent glutamate sources and endogenous co-agonists activate extrasynaptic NMDA receptors on amacrine cells of the rod pathway microcircuiten_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 The Authorsen_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1111/ejn.15325
dc.identifier.cristin1918283
dc.source.journalEuropean Journal of Neuroscienceen_US
dc.source.pagenumber4456-4474en_US
dc.relation.projectNorges forskningsråd: 261914en_US
dc.relation.projectNorges forskningsråd: 213776en_US
dc.subject.nsiVDP::Basale biofag: 470en_US
dc.subject.nsiVDP::Basic biosciences: 470en_US
dc.identifier.citationEuropean Journal of Neuroscience. 2021, 54 (2), 4456-4474.en_US
dc.source.volume54en_US
dc.source.issue2en_US


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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