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Altered Synaptic and Extrasynaptic NMDA Receptor Properties in Substantia Nigra Dopaminergic Neurons From Mice Lacking the GluN2D Subunit.

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cam.issuedOnline2018-10-11
dc.contributor.authorMorris, Paul G
dc.contributor.authorMishina, Masayoshi
dc.contributor.authorJones, Susan
dc.contributor.orcidMorris, Paul G [0000-0002-4554-2132]
dc.date.accessioned2018-12-04T00:30:38Z
dc.date.available2018-12-04T00:30:38Z
dc.date.issued2018
dc.description.abstractN-methyl-D-aspartate receptors (NMDARs) are ubiquitously expressed in the mammalian brain and are essential for neuronal development, survival and plasticity. GluN2 subunit composition has a profound effect on the properties of NMDARs. In substantia nigra dopaminergic (SNc-DA) neurons, pharmacological experiments suggest that the relatively rare GluN2D subunits form functional synaptic and extrasynaptic NMDARs. Given the importance of establishing this point, mice lacking the GluN2D subunit (Grin2D-null) were used in this study to further explore the contribution of the GluN2D subunit to NMDAR responses. Significantly less DQP-1105-sensitive NMDAR-EPSC and significantly more ifenprodil-sensitive NMDAR-EPSC was observed in SNc-DA neurons from Grin2D-null mice, indicating that in these animals a small population of synaptic GluN2D subunits is replaced with GluN2B. Significantly larger currents were seen in response to higher concentrations (1-10 mM) of NMDA in SNc-DA neurons from Grin2D-null mice, as well as significantly more desensitization: these data are consistent with the presence of GluN2D-containing whole-cell NMDARs in SNc-DA neurons, with low conductance and little desensitization. Brief applications of NMDA evoked responses that were significantly less sensitive to DQP-1105 in slices from Grin2D-null mice. Tonic NMDAR activity in response to ambient extracellular glutamate, determined by the sensitivity of tonic current to D-AP5 (50 μM), was significantly less in SNc-DA neurons from Grin2D-null mice. In the presence of the glutamate transporter blocker TBOA (30 μM), the D-AP5-sensitive current was also significantly less in Grin2D-null mice. Taken together, these data support the evidence for GluN2D subunit expression in functional NMDARs at both synaptic and extrasynaptic locations in SNc-DA neurons.
dc.description.sponsorshipThe Wellcome Trust (092611/B/10/Z) BBSRC DTP Studentship to PGM
dc.format.mediumElectronic-eCollection
dc.identifier.doi10.17863/CAM.33559
dc.identifier.eissn1662-5102
dc.identifier.issn1662-5102
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286247
dc.languageeng
dc.language.isoeng
dc.publisherFrontiers Media SA
dc.publisher.urlhttp://dx.doi.org/10.3389/fncel.2018.00354
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectGluN2B subunit
dc.subjectGluN2D subunit
dc.subjectNMDA receptor
dc.subjectNMDAR-EPSC
dc.subjectdopamine neuron
dc.subjectsubstantia nigra
dc.subjecttonic NMDAR current
dc.titleAltered Synaptic and Extrasynaptic NMDA Receptor Properties in Substantia Nigra Dopaminergic Neurons From Mice Lacking the GluN2D Subunit.
dc.typeArticle
dcterms.dateAccepted2018-09-20
prism.publicationDate2018
prism.publicationNameFront Cell Neurosci
prism.startingPage354
prism.volume12
pubs.funder-project-idWellcome Trust (092611/B/10/Z)
rioxxterms.licenseref.startdate2018-01
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3389/fncel.2018.00354

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