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AuthorBygrave, Alexei
AuthorKullmann, Dimitri
AuthorBannerman, David
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AbstractHypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs), whether caused by endogenous factors like auto-antibodies or mutations, or by pharmacological or genetic manipulations, produces a wide variety of deficits which overlap with—but do not precisely match—the symptom spectrum of schizophrenia. In order to understand how NMDAR hypofunction leads to different components of the syndrome, it is necessary to take into account which neuronal subtypes are particularly affected by it in terms of detrimental functional alterations. We provide a comprehensive overview detailing findings in rodent models with cell type–specific knockout of NMDARs. Regarding inhibitory cortical cells, an emerging model suggests that NMDAR hypofunction in parvalbumin (PV) positive interneurons is a potential risk factor for this disease. PV interneurons display a selective vulnerability resulting from a combination of genetic, cellular, and environmental factors that produce pathological multi-level positive feedback loops. Central to this are two antioxidant mechanisms—NMDAR activity and perineuronal nets—which are themselves impaired by oxidative stress, amplifying disinhibition. However, NMDAR hypofunction in excitatory pyramidal cells also produces a range of schizophrenia-related deficits, in particular maladaptive learning and memory recall. Furthermore, NMDAR blockade in the thalamus disturbs thalamocortical communication, and NMDAR ablation in dopaminergic neurons may provoke over-generalization in associative learning, which could relate to the positive symptom domain. Therefore, NMDAR hypofunction can produce schizophrenia-related effects through an action on various different circuits and cell types.dc.description.abstract
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license text
KeywordN-methyl-D-aspartate receptor hypofunctiondc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHPsychotic disordersdc.subject.mesh
MeSHReceptors, N-Methyl-D-Aspartatedc.subject.mesh
MeSHDizocilpine maleatedc.subject.mesh
MeSHSchizophrenia, Catatonicdc.subject.mesh
TitleCan N-Methyl-D-Aspartate receptor hypofunction in schizophrenia be localized to an Individual cell type?dc.title
Resource typeWissenschaftlicher Artikeldc.type
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionInstitut für Angewandte Physiologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeCollectionuulm.typeDCMI
In cooperation withJohns Hopkins University, Baltimoreuulm.cooperation
In cooperation withUniversity College London, Londonuulm.cooperation
In cooperation withUniversity of Oxforduulm.cooperation
DOI of original publication10.3389/fpsyt.2019.00835dc.relation1.doi
Source - Title of sourceFrontiers in Psychiatrysource.title
Source - Place of publicationFrontiers Media S.A.source.publisher
Source - Volume10source.volume
Source - Year2019source.year
Source - Article number835source.articleNumber
Source - eISSN1664-0640source.identifier.eissn
FundingSir Henry Wellcome Postdoctoral Fellowship of the Wellcome Trust [098896]uulm.funding
FundingOXION programme of the Wellcome Trustuulm.funding
FundingLandesgraduiertenförderung des Landes Baden-Württemberg, Germany (LGFG)uulm.funding
FundingJohn Fell Fund of the Oxford University Pressuulm.funding
FundingMedical Research Counciluulm.funding
FundingWellcome Investigator Awarduulm.funding
FundingDFG [KA/4594/2-1]uulm.funding
FundingUlm Universityuulm.funding
University Bibliographyjauulm.unibibliographie

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CC BY 4.0 International
Except where otherwise noted, this item's license is described as CC BY 4.0 International